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  • 1
    Language: English
    In: Brain Research, Jan 12, 2011, Vol.1368, p.346(9)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.brainres.2010.10.067 Byline: Li Sun, Wei Zhou, Sabine Heiland, Hugo H. Marti, Roland Veltkamp Keywords: Cerebral ischemia; Thrombolysis; Secondary hemorrhage; Reperfusion; Blood-brain barrier damage Abstract: Secondary hemorrhage after thrombolysis in ischemic stroke is an important complication, which has been difficult to study in preclinical disease models. We have established and characterized a model of thromboembolic middle cerebral artery occlusion in rats. Advantages of this model include a very low rate of spontaneous recanalization and good reperfusion after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). In vivo T2* MR imaging and postmortem assays were used for quantification of secondary brain hemorrhage. In our protocol, 12 thrombin-induced autologous blood clots are injected into the internal carotid artery. No spontaneous reperfusion occurs in the first 24h. However, injection of rt-PA 2 or 4h thereafter leads to reperfusion of the MCA territory consistent infarcts, increased blood-brain barrier permeability, and secondary hemorrhage. Remarkably, clinically important factors known to affect the extent and likelihood of secondary hemorrhage such as hypertension and delayed onset of thrombolysis also increase hematoma size in the model. Thus, the model may serve to investigate the pathophysiology of thrombolysis-induced hemorrhage in thromboembolic ischemia as well as potential adjunctive therapies to prevent this complication. Article History: Accepted 16 October 2010
    Keywords: Thromboembolism -- Models ; Permeability -- Models ; Stroke -- Models ; Hemorrhage -- Models
    ISSN: 0006-8993
    Source: Cengage Learning, Inc.
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  • 2
    Language: English
    In: Brain Research, March 12, 2010, Vol.1320, p.135(8)
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.brainres.2010.01.015 Byline: Sergio Illanes (a)(b)(c), Wei Zhou (a), Sabine Heiland (d), Zorn Markus (e), Roland Veltkamp (a) Keywords: Experimental stroke; Hematoma expansion; Intracerebral hemorrhage; MRI; Oral anticoagulant; Stroke model Abbreviations: ICH, Intracerebral hemorrhage; OAC-ICH, Oral anticoagulants associated intracerebral hemorrhage; INR, International normalized ratio; PCC, Prothrombin concentrate; PoC, Point of care INR assay; TVBT, Tail vein bleeding time Abstract: The burden of intracerebral hemorrhage associated with oral anticoagulants (OAC-ICH) is growing. However, little is known about the pathophysiology of W-ICH. Herein, we refine a mouse model of OAC-ICH using repetitive T2* MRI to describe kinetics of hematoma enlargement, and establish a benchside point of care INR assay (PoC) for assessment of anticoagulation. Author Affiliation: (a) Department of Neurology, University Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany (b) UTAC, Hospital Clinico Universidad de Chile, Santos Dumont 999, Santiago, Chile (c) ICU Clinica Davila, Recoleta 464, Santiago, Chile (d) Department of Neuroradiology, University Heidelberg, Im Neuenheimer Feld 400 69120, Germany (e) Central Laboratory, University Heidelberg, Im Neuenheimer Feld 671 69120, Germany Article History: Accepted 6 January 2010
    Keywords: Intracerebral Hemorrhage -- Analysis ; Thrombin -- Analysis ; Universities And Colleges -- Analysis ; Hematoma -- Analysis ; Anticoagulants -- Analysis ; Prothrombin -- Analysis
    ISSN: 0006-8993
    Source: Cengage Learning, Inc.
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  • 3
    In: Stroke, 2011, Vol.42(1), pp.191-195
    Description: BACKGROUND AND PURPOSE—: Intracerebral hemorrhage associated with oral anticoagulants has a poor prognosis. Current treatment guidelines are based on case series and plausibility only, and a common consensus on effective hemostatic therapy is missing. We compared the effectiveness of diverse hemostatic approaches in a mouse model of warfarin-associated intracerebral hemorrhage. METHODS—: Male C57BL/6 mice received anticoagulant treatment with warfarin (0.4 mg/kg for 3 days). Intracerebral hemorrhage was induced by striatal injection of collagenase, and 30 minutes later, mice received an intravenous injection of saline (200 μL n=15), prothrombin complex concentrate (100 U/kg, n=10), fresh-frozen plasma (200 μL, n=13), recombinant human Factor VII activated (3.5 mg/kg, n=8 and 10 mg/kg, n=8), or tranhexamic acid (400 mg/kg, n=12). Intracerebral hemorrhage volume was quantified on T2-weighted images after 24 hours. RESULTS—: Mean hematoma volumes were 7.4±1.8 mm in the nonwarfarin controls and 21.9±5.0 mm in the warfarin group receiving saline. Prothrombin complex concentrate (7.5±2.3 mm) and fresh-frozen plasma (8.7±2.1) treatment resulted in significantly smaller hematoma volume compared with saline. Recombinant human Factor VII activated (10 mg/kg: 14.7±3.4; 3.5 mg/kg: 15.0±6.8 mm) and tranexamic acid (16.2±4.1 mm) were less effective. Water content in the hemorrhagic hemisphere was similar in all groups except for tranexamic acid in which it was significantly increased. CONCLUSIONS—: Prothrombin complex concentrate and fresh-frozen plasma effectively prevent hematoma growth in murine warfarin-associated intracerebral hemorrhage, whereas Factor VIIa was less effective. Tranexamic acid exacerbates perihematoma edema in this mouse warfarin-associated intracerebral hemorrhage model.
    Keywords: Intravenous Administration ; Anticoagulants ; Collagenase ; Stroke ; Prognosis ; Animal Models ; Coagulation Factors ; Edema ; Warfarin ; Hemorrhage ; Coagulation Factor Viia ; Water Content ; Hematoma ; Prothrombin ; Neostriatum ; Neurology & Neuropathology;
    ISSN: 0039-2499
    ISSN: 15244628
    E-ISSN: 15244628
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  • 4
    In: PLoS ONE, 2015, Vol.10(12)
    Description: Introduction T2 relaxometry has become an important tool in quantitative MRI. Little focus has been put on the effect of the refocusing flip angle upon the offset parameter, which was introduced to account for a signal floor due to noise or to long T2 components. The aim of this study was to show that B1 imperfections contribute significantly to the offset . We further introduce a simple method to reduce the systematic error in T2 by discarding the first echo and using the offset fitting approach. Materials and Methods Signal curves of T2 relaxometry were simulated based on extended phase graph theory and evaluated for 4 different methods (inclusion and exclusion of the first echo, while fitting with and without the offset ). We further performed T2 relaxometry in a phantom at 9.4T magnetic resonance imaging scanner and used the same methods for post-processing as in the extended phase graph simulated data. Single spin echo sequences were used to determine the correct T2 time. Results The simulation data showed that the systematic error in T2 and the offset depends on the refocusing pulse, the echo spacing and the echo train length. The systematic error could be reduced by discarding the first echo. Further reduction of the systematic T2 error was reached by using the offset as fitting parameter. The phantom experiments confirmed these findings. Conclusion The fitted offset parameter in T2 relaxometry is influenced by imperfect refocusing pulses. Using the offset as a fitting parameter and discarding the first echo is a fast and easy method to minimize the error in T2, particularly for low to intermediate echo train length.
    Keywords: Research Article
    E-ISSN: 1932-6203
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  • 5
    Language: English
    In: PLoS ONE, 01 January 2014, Vol.9(11), p.e110727
    Description: PURPOSE: To analyze if tumor vessels can be visualized, segmented and quantified in glioblastoma patients with time of flight (ToF) angiography at 7 Tesla and multiscale vessel enhancement filtering. MATERIALS AND METHODS: Twelve patients with newly diagnosed glioblastoma were examined with ToF angiography (TR = 15 ms, TE = 4.8 ms, flip angle = 15°, FOV = 160 × 210 mm(2), voxel size: 0.31 × 0.31 × 0.40 mm(3)) on a whole-body 7 T MR system. A volume of interest (VOI) was placed within the border of the contrast enhancing part on T1-weighted images of the glioblastoma and a reference VOI was placed in the non-affected contralateral white matter. Automated segmentation and quantification of vessels within the two VOIs was achieved using multiscale vessel enhancement filtering in ImageJ. RESULTS: Tumor vessels were clearly visible in all patients. When comparing tumor and the reference VOI, total vessel surface (45.3 ± 13.9 mm(2) vs. 29.0 ± 21.0 mm(2) (p〈0.035)) and number of branches (3.5 ± 1.8 vs. 1.0 ± 0.6 (p〈0.001) per cubic centimeter were significantly higher, while mean vessel branch length was significantly lower (3.8 ± 1.5 mm vs 7.2 ± 2.8 mm (p〈0.001)) in the tumor. DISCUSSION: ToF angiography at 7-Tesla MRI enables characterization and quantification of the internal vascular morphology of glioblastoma and may be used for the evaluation of therapy response within future studies.
    Keywords: Sciences (General)
    E-ISSN: 1932-6203
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  • 6
    Language: English
    In: 2012, Vol.7(11), p.e49742
    Description: Patients with ulnar neuropathy of unclear etiology occasionally present with lesion extension from elbow to upper arm level on MRI. This study investigated whether MRI thereby distinguishes multifocal neuropathy from focal-compressive neuropathy at the elbow. ; This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 122 patients with ulnar mononeuropathy of undetermined localization and etiology by clinical and electrophysiological examination were assessed by MRI at upper arm and elbow level using T2-weighted fat-saturated sequences at 3T. Twenty-one patients were identified with proximal ulnar nerve lesions and evaluated for findings suggestive of disseminated neuropathy (i) subclinical lesions in other nerves, (ii) unfavorable outcome after previous decompressive elbow surgery, and (iii) subsequent diagnosis of inflammatory or other disseminated neuropathy. Two groups served as controls for quantitative analysis of nerve-to-muscle signal intensity ratios: 20 subjects with typical focal ulnar neuropathy at the elbow and 20 healthy subjects. ; In the group of 21 patients with proximal ulnar nerve lesion extension, T2-w ulnar nerve signal was significantly (p〈0.001) higher at upper arm level than in both control groups. A cut-off value of 1.92 for maximum nerve-to-muscle signal intensity ratio was found to be sensitive (86%) and specific (100%) to discriminate this group. Ten patients (48%) exhibited additional T2-w lesions in the median and/or radial nerve. Another ten (48%) had previously undergone elbow surgery without satisfying outcome. Clinical follow-up was available in 15 (71%) and revealed definitive diagnoses of multifocal neuropathy of various etiologies in four patients. In another eight, diagnoses could not yet be considered definitive but were consistent with multifocal neuropathy. ; Proximal ulnar nerve T2 lesions at upper arm level are detected by MRI and indicate the presence of a non-focal disseminated neuropathy instead of a focal compressive neuropathy.
    Keywords: Research Article ; Biology ; Medicine ; Immunology ; Physiology ; Neurological Disorders ; Radiology And Medical Imaging
    E-ISSN: 1932-6203
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  • 7
    Language: English
    In: NeuroImage, 01 November 2016, Vol.141, pp.81-87
    Description: To develop an in-vivo imaging method for the measurement of dorsal-root-ganglia-(DRG) perfusion, to establish its normal values in patients without known peripheral nerve disorders or radicular pain syndromes and to determine the physiological spatial perfusion pattern within the DRG. This prospective study was approved by the institutional ethics committee and written informed consent was obtained from all participants. 46 (24 female, 22 male, mean age 46.0 ± 15.2 years) subjects without known peripheral neuropathies or pain syndromes were examined by a 3 Tesla MRI scanner (Magnetom VERIO or TRIO, Siemens AG, Erlangen, Germany) with a VIBE (Volume-Interpolated-Breathhold-Examination) dynamic-contrast-enhanced (DCE) T1-w-sequence (TR/TE 3.3/1.11 ms; 24 slices; voxel resolution 1.3 × 1.3 × 3.0 mm ) covered the pelvis from the upper plate of the 5th lumbar vertebra to the 2nd sacral vertebra. Transfer-constant (K ) and interstitial-volume-fraction (interstitial-leakage-fraction, V ) were modeled for the DRG and spinal nerve by applying the Tofts-model. Statistical analyses included pairwise comparisons of L5/S1 DRG vs. spinal nerve. Furthermore, distinct physiological zones within the S1 DRG were compared ( (CBRA) vs. (NFRA)). DRG showed a significantly increased permeability compared to spinal nerve (K 3.8 ± 1.5 10 /min vs. 1.6 ± 0.9 10 /min, p-value: 〈 0.001) combined with an increased interstitial leakage of contrast agent into the extravascular-extracellular-space (V 38.1 ± 19.2% vs. 17.3 ± 9.9%, p-value: 〈 0.001). Parameters showed no statistically significant difference on DRG-level (L5 vs. S1; p-value: 0.62 (K ); 0.17 (V )) and -side (left vs. right; p-value: 0.25 (K ); 0.79 (V )). Female gender was associated with a significantly increased permeability (K female 4.3 ± 1.4 10 /min vs. male 3.4 ± 0.9 10 /min, p-value: 〈 0.05) but no statistically significant differences in interstitial leakage (V female 40.1 ± 14,1% vs. male 34.5 ± 17.4%, p-value: 0.24). DRG showed distinct spatial distribution patterns of perfusion: K and V were significantly higher in the CBRA than in the NFRA (K 4.4 ± 1.8 10 /min vs. 1.7 ± 1.2 10 /min, p-value: 〈 0.001 and V 40.9 ± 21.3% vs. 15.1 ± 11.7%, p-value: 〈 0.001). Non-invasive and in-vivo measurement of human DRG perfusion by MRI is a feasible technique. DRG show substantially higher permeability and interstitial leakage than spinal nerves. Even distinct physiological perfusion patterns for different microstructural compartments could be observed within the DRG. The technique may become particularly useful for future research on the poorly understood human sensory neuropathies and pain syndromes.
    Keywords: Dorsal Root Ganglia ; Dce-Mri ; Perfusion ; Permeability ; Polyneuropathy ; Medicine
    ISSN: 1053-8119
    E-ISSN: 1095-9572
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  • 8
    Language: English
    In: NeuroImage, 15 February 2018, Vol.167, pp.178-190
    Description: Ambiguous and masked stimuli have been used to study conscious perception by comparing neural activity during different percepts of identical physical stimuli. One limitation of this approach is that it typically requires a reporting task that may engage neural processes beyond those required for conscious perception. Here, we explored potential fMRI correlates of auditory conscious perception with and without overt report. In experiment 1, regular tone patterns were presented as targets under informational masking, and participants reported their percepts on each trial. In experiment 2, regular tone patterns were presented without masking, while the uninformed participants (i) passively fixated, (ii) performed an orthogonal visual task, and (iii) reported trial-wise the presence of the auditory pattern as in experiment 1 (in fixed order). Under informational masking, target-pattern detection was associated with activity in auditory cortex, superior temporal sulcus, and a distributed fronto-parieto-insular network. Unmasked and task-irrelevant tone patterns elicited activity that overlapped with the network observed under informational masking in auditory cortex, the right superior temporal sulcus, and the ventral precentral sulcus in an ROI analysis. We therefore consider these structures candidate regions for a neural substrate of auditory conscious perception. In contrast, activity in the intraparietal sulcus, insula, and dorsal precentral sulcus were only observed for unmasked tone patterns when they were task relevant. These areas therefore appear more closely related to task performance or top-down attention rather than auditory conscious perception, .
    Keywords: Auditory Cortex ; Awareness ; Superior Temporal Sulcus ; Ventral Attention System ; Dorsal Attention System ; Medicine
    ISSN: 1053-8119
    E-ISSN: 1095-9572
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  • 9
    Language: English
    In: Brain Research, 2011, Vol.1368, pp.346-354
    Description: Secondary hemorrhage after thrombolysis in ischemic stroke is an important complication, which has been difficult to study in preclinical disease models. We have established and characterized a model of thromboembolic middle cerebral artery occlusion in rats. Advantages of this model include a very low rate of spontaneous recanalization and good reperfusion after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). In vivo T2* MR imaging and postmortem assays were used for quantification of secondary brain hemorrhage. In our protocol, 12 thrombin-induced autologous blood clots are injected into the internal carotid artery. No spontaneous reperfusion occurs in the first 24 h. However, injection of rt-PA 2 or 4 h thereafter leads to reperfusion of the MCA territory consistent infarcts, increased blood–brain barrier permeability, and secondary hemorrhage. Remarkably, clinically important factors known to affect the extent and likelihood of secondary hemorrhage such as hypertension and delayed onset of thrombolysis also increase hematoma size in the model. Thus, the model may serve to investigate the pathophysiology of thrombolysis-induced hemorrhage in thromboembolic ischemia as well as potential adjunctive therapies to prevent this complication. ► A model reflects secondary hemorrhage after thrombolysis in cerebral ischemia. ► It causes consistent vascular occlusion without spontaneous reperfusion. ► The injection of rt-PA induces good reperfusion in the MCA territory. ► Delayed thrombolysis, artery hypertention, and reperfusion increase secondary hemorrhage.
    Keywords: Cerebral Ischemia ; Thrombolysis ; Secondary Hemorrhage ; Reperfusion ; Blood–Brain Barrier Damage ; Anatomy & Physiology
    ISSN: 0006-8993
    E-ISSN: 1872-6240
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  • 10
    Language: English
    In: Brain research, 2011, Vol.1368, pp.346-354
    Description: Secondary hemorrhage after thrombolysis in ischemic stroke is an important complication, which has been difficult to study in preclinical disease models. We have established and characterized a model of thromboembolic middle cerebral artery occlusion in rats. Advantages of this model include a very low rate of spontaneous recanalization and good reperfusion after intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). In vivo T2* MR imaging and postmortem assays were used for quantification of secondary brain hemorrhage. In our protocol, 12 thrombin-induced autologous blood clots are injected into the internal carotid artery. No spontaneous reperfusion occurs in the first 24h. However, injection of rt-PA 2 or 4h thereafter leads to reperfusion of the MCA territory consistent infarcts, increased blood–brain barrier permeability, and secondary hemorrhage. Remarkably, clinically important factors known to affect the extent and likelihood of secondary hemorrhage such as hypertension and delayed onset of thrombolysis also increase hematoma size in the model. Thus, the model may serve to investigate the pathophysiology of thrombolysis-induced hemorrhage in thromboembolic ischemia as well as potential adjunctive therapies to prevent this complication. ; p. 346-354.
    Keywords: Blood ; Pathophysiology ; Carotid Arteries ; Hematoma ; Stroke ; Blood-Brain Barrier ; Intravenous Injection ; Disease Models ; Hypertension ; Ischemia ; T-Plasminogen Activator ; Brain ; Rats ; Image Analysis ; Permeability
    ISSN: 0006-8993
    Source: AGRIS (Food and Agriculture Organization of the United Nations)
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