Wolf-Dieter Heiss

Cornell University, Ithaca, New York, United States

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Publications (220)541.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Non-invasive brain stimulation such as repetitive transcranial magnetic stimulation (rTMS) or transcranial direct current stimulation (tDCS) has been used in case series and small randomized controlled trials to improve recovery from post-stroke aphasia in combination with speech and language therapy. Results of these studies suggest possible clinical efficacy and an excellent safety profile. Therefore a larger international multicenter proof-of-concept trial was launched, to directly compare the safety and efficacy of rTMS, tDCS and sham stimulation as adjuvant therapy to SLT in sub-acute post-stroke aphasia. In the 4 participating centers, sub-acute stroke patients with aphasia are randomized between 5 and 30 days after ischemic stroke to either receive rTMS, tDCS or sham stimulation in combination with a daily 45 minute speech and language therapy session for 10 days. Efficacy is evaluated at 1 and 30 days after the last of the 10 treatment sessions using three outcome measures, validated in all participating languages: Boston naming test, Token test and Verbal fluency test. Additionally, adverse events are recorded to prove safety. In this study a total of 90 patients will be recruited and data analysis will be completed in 2016. This is the first multilingual and multinational randomized and controlled trial in post-stroke aphasia and if positive, will add an effective new strategy for early-stage post-stroke aphasia rehabilitation.
    Journal of Stroke and Cerebrovascular Diseases 11/2014; · 1.99 Impact Factor
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    ABSTRACT: Cerebral blood flow (CBF) and extent of irreversible tissue damage as well as the time course of extracellular concentration of amino acids, substrates of energy metabolism, and purine metabolites, intracranial pressure and tissue oxygen tension were assessed in 34 patients with large strokes covering more than 50% of the MCA territory. The results were compared to findings in the experimental model of transient (for 3 hours) MCA occlusion in cats. In the experimental model as well as in the clinical setting development of malignant brain infarcts (due to formation of space occupying brain edema) was predicted by the size of critically hypoperfused tissue and the volume of irreversibly damaged tissue. The course of malignant infarcts was characterized by progressive increase in concentrations of excitatory amino acids, lactate, pyruvate, glycerol, hypoxanthine and in intracranial pressure, while cerebral perfusion pressure and tissue oxygen tension decreased. These results clearly differentiate a malignant from a benign course of large hemispheric infarction. The methods can be used to identify patients at risk for formation of space occupying edema and to select patients who could benefit from invasive therapeutic strategies.
    Acta Neurochirurgica 08/2014; · 1.79 Impact Factor
  • Stroke 07/2014; 45(9). · 6.02 Impact Factor
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    ABSTRACT: Severe atherosclerosis in the aortic arch is associated with a high risk of recurrent vascular events, but the optimal antithrombotic strategy is unclear. This prospective randomized controlled, open-labeled trial, with blinded end point evaluation (PROBE design) tested superiority of aspirin 75 to 150 mg/d plus clopidogrel 75 mg/d (A+C) over warfarin therapy (international normalized ratio 2-3) in patients with ischemic stroke, transient ischemic attack, or peripheral embolism with plaque in the thoracic aorta >4 mm and no other identified embolic source. The primary end point included cerebral infarction, myocardial infarction, peripheral embolism, vascular death, or intracranial hemorrhage. Follow-up visits occurred at 1 month and then every 4 months post randomization. The trial was stopped after 349 patients were randomized during a period of 8 years and 3 months. After a median follow-up of 3.4 years, the primary end point occurred in 7.6% (13/172) and 11.3% (20/177) of patients on A+C and on warfarin, respectively (log-rank, P=0.2). The adjusted hazard ratio was 0.76 (95% confidence interval, 0.36-1.61; P=0.5). Major hemorrhages including intracranial hemorrhages occurred in 4 and 6 patients in the A+C and warfarin groups, respectively. Vascular deaths occurred in 0 patients in A+C arm compared with 6 (3.4%) patients in the warfarin arm (log-rank, P=0.013). Time in therapeutic range (67% of the time for international normalized ratio 2-3) analysis by tertiles showed no significant differences across groups. Because of lack of power, this trial was inconclusive and results should be taken as hypothesis generating. http://www.clinicaltrials.gov. Unique identifier: NCT00235248.
    Stroke 04/2014; · 6.02 Impact Factor
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    ABSTRACT: Background: Accumulating evidence from single case studies, small case series and randomized controlled trials seems to suggest that inhibitory noninvasive brain stimulation (NIBS) over the contralesional inferior frontal gyrus (IFG) of right-handers in conjunction with speech and language therapy (SLT) improves recovery from poststroke aphasia. Application of inhibitory NIBS to improve recovery in left-handed patients has not yet been reported. Methods: A total of 29 right-handed subacute poststroke aphasics were randomized to receive either 10 sessions of SLT following 20 min of inhibitory repetitive transcranial magnetic stimulation (rTMS) over the contralesional IFG or 10 sessions of SLT following sham stimulation; 2 left-handers were treated according to the same protocol with real rTMS. Language activation patterns were assessed with positron emission tomography prior to and after the treatment; 95% confidence intervals for changes in language performance scores and the activated brain volumes in both hemispheres were derived from TMS- and sham-treated right-handed patients and compared to the same parameters in left-handers. Results: Right-handed patients treated with rTMS showed better recovery of language function in global aphasia test scores (t test, p < 0.002) as well as in picture-naming performance (ANOVA, p = 0.03) than sham-treated right-handers. In treated right-handers, a shift of activation to the ipsilesional hemisphere was observed, while sham-treated patients consolidated network activity in the contralesional hemisphere (repeated-measures ANOVA, p = 0.009). Both left-handed patients also improved, with 1 patient within the confidence limits of TMS-treated right-handers (23 points, 15.9-28.9) and the other patient within the limits of sham-treated subjects (8 points, 2.8-14.5). Both patients exhibited only a very small interhemispheric shift, much less than expected in TMS-treated right-handers, and more or less consolidated initially active networks in both hemispheres. Conclusion: Inhibitory rTMS over the nondominant IFG appears to be a safe and effective treatment for right-handed poststroke aphasics. In the 2 cases of left-handed aphasics no deterioration of language performance was observed with this protocol. However, therapeutic efficiency is less obvious and seems to be more related to the dominance pattern prior to the stroke than to the TMS intervention. © 2013 S. Karger AG, Basel.
    Cerebrovascular Diseases 11/2013; 36(5-6):363-372. · 3.70 Impact Factor
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    ABSTRACT: Modulation of activity in language networks using repetitive transcranial magnetic stimulation (rTMS) may possibly support recovery from poststroke aphasia. Case series and feasibility studies seem to indicate a therapeutic effect; however, randomized sham-controlled, proof-of-principle studies relating clinical effects to activation patterns are missing. Twenty-four patients with subacute poststroke aphasia were randomized to a 10-day protocol of 20-minute inhibitory 1 Hz rTMS over the right triangular part of the posterior inferior frontal gyrus or sham stimulation, followed by 45 minutes of speech and language therapy. Activity in language networks was measured with O-15-water positron emission tomography during verb generation before and after treatment. Language performance was assessed using the Aachen Aphasia Test battery. The primary outcome measure, global Aachen Aphasia Test score change, was significantly higher in the rTMS group (t test, P=0.003). Increases were largest for subtest naming (P=0.002) and tended to be higher for comprehension, token test, and writing (P<0.1). Patients in the rTMS group activated proportionally more voxels in the left hemisphere after treatment than before (difference in activation volume index) compared with sham-treated patients (t test, P=0.002).There was a moderate but significant linear relationship between activation volume index change and global Aachen Aphasia Test score change (r(2)=0.25; P=0.015). Ten sessions of inhibitory rTMS over the right posterior inferior frontal gyrus, in combination with speech and language therapy, significantly improve language recovery in subacute ischemic stroke and favor recruitment of left-hemispheric language networks.
    Stroke 06/2013; · 6.02 Impact Factor
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    ABSTRACT: Cerebrolysin showed neuroprotective and neurotrophic properties in various preclinical models of ischemia and small clinical trials. The aim of this large double-blind, placebo-controlled randomized clinical trial was to test its efficacy and safety in patients with acute ischemic stroke. Patients with acute ischemic hemispheric stroke were randomized within 12 hours of symptoms onset to active treatment (30 mL Cerebrolysin daily) or placebo (saline solution) given as intravenous infusion for 10 days in addition to aspirin (100 mg daily). The patients were followed up to 90 days. The primary end point was the result of a combined global directional test of modified Rankin Scale, Barthel Index, and National Institutes of Health Stroke Scale. Adverse events were documented to assess safety. A total of 1070 patients were enrolled in this study. Five hundred twenty-nine patients were assigned to Cerebrolysin and 541 to placebo. The confirmatory end point showed no significant difference between the treatment groups. When stratified by severity however, a post hoc analysis of National Institutes of Health Stroke Scale and modified Rankin Scale showed a trend in favor of Cerebrolysin in patients with National Institutes of Health Stroke Scale >12 (National Institutes of Health Stroke Scale: OR, 1.27; CI lower bound, 0.97; modified Rankin Scale: OR, 1.27; CI lower bound, 0.90). In this subgroup, the cumulative mortality by 90 days was 20.2% in the placebo and 10.5% in the Cerebrolysin group (hazard ratio, 1.9661; CI lower bound, 1.0013). In this study, the confirmatory end point showed neutral results between the treatment groups. However, a favorable outcome trend was seen in the severely affected patients with ischemic stroke treated with Cerebrolysin. This observation should be confirmed by a further clinical trial. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00868283.
    Stroke 03/2012; 43(3):630-6. · 6.02 Impact Factor
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    ABSTRACT: Perfusion-weighted imaging maps are used to identify critical hypoperfusion in acute stroke. However, quantification of perfusion may depend on the choice of the arterial input function (AIF). Using quantitative positron emission tomography we evaluated the influence of the AIF location on maps of absolute and relative perfusion-weighted imaging to detect penumbral flow (PF; <20 mL/100 g/min on positron emission tomography(CBF)) in acute stroke. In 22 patients with acute stroke the AIF was placed at 7 sites (M1, M2, M3 ipsi- and contralateral and internal carotid artery-M1 contralateral to the infarct). Comparative (15)O-water positron emission tomography and AIF-dependent perfusion-weighted imaging (cerebral blood flow, cerebral blood volume, mean transit time, and time to maximum) were performed. A receiver operating characteristic curve analysis described the threshold independent performance (area under the curve) of the perfusion-weighted maps for all 7 AIF locations and identified the best AIF-dependent absolute and relative thresholds to identify PF. These results were compared with AIF-independent time-to-peak maps. Quantitative perfusion-weighted imaging maps of cerebral blood flow and time to maximum performed best. For PF detection, AIF placement did significantly influence absolute PF thresholds. However, AIF placement did not influence (1) the threshold independent performance; and (2) the relative PF thresholds. AIF placement in the proximal segment of the contralateral middle cerebral artery (cM1) was preferable for quantification. AIF-based maps of cerebral blood flow and time to maximum were most accurate to detect the PF threshold. The AIF placement significantly altered absolute PF thresholds and showed best agreement with positron emission tomography for the cM1 segment. The performance of relative PF thresholds, however, was not AIF location-dependent and might be along with AIF-independent time-to-peak maps, more suitable than absolute PF thresholds in acute stroke if detailed postprocessing is not feasible.
    Stroke 12/2011; 43(2):378-85. · 6.02 Impact Factor
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    Wolf-Dieter Heiss, Peter Raab, Heinrich Lanfermann
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    ABSTRACT: Neuroimaging plays a significant role in the diagnosis of intracranial tumors, especially brain gliomas, and must consist of an assessment of location and extent of the tumor and of its biologic activity. Therefore, morphologic imaging modalities and functional, metabolic, or molecular imaging modalities should be combined for primary diagnosis and for following the course and evaluating therapeutic effects. MRI is the gold standard for providing detailed morphologic information and can supply some additional insights into metabolism (MR spectroscopy) and perfusion (perfusion-weighted imaging) but still has limitations in identifying tumor grade, invasive growth into neighboring tissue, and treatment-induced changes, as well as recurrences. These insights can be obtained by various PET modalities, including imaging of glucose metabolism, amino acid uptake, nucleoside uptake, and hypoxia. Diagnostic accuracy can benefit from coregistration of PET results and MRI, combining the high-resolution morphologic images with the biologic information. These procedures are optimized by the newly developed combination of PET and MRI modalities, permitting the simultaneous assessment of morphologic, functional, metabolic, and molecular information on the human brain.
    Journal of Nuclear Medicine 08/2011; 52(10):1585-600. · 5.56 Impact Factor
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    ABSTRACT: Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PET) cameras. However, the high-resolution research tomograph (HRRT) PET system has a resolution of 2 mm, sufficient for the investigation of important structures such as the pallidum and thalamic subnuclei. Using the HRRT, we performed [(18)F]-fluorodeoxyglucose (FDG) scans on 21 patients with PD and 11 age-matched controls. We employed three types of normalization: white matter, global mean, and data-driven normalization. We performed volume-of-interest analyses of small subcortical gray matter structures. Voxel-based comparisons were performed to investigate the extent of cortical hypometabolism. The most significant level of relative subcortical hypermetabolism was detected in the external pallidum (GPe), irrespective of normalization strategy. Hypermetabolism was suggested also in the internal pallidum, thalamic subnuclei, and the putamen. Widespread cortical hypometabolism was seen in a pattern very similar to previously reported patterns in patients with PD. The presence and extent of subcortical hypermetabolism in PD is dependent on type of normalization. However, the present findings suggest that PD, in addition to widespread cortical hypometabolism, is probably characterized by true hypermetabolism in the GPe. This finding was predicted by the animal 2-deoxyglucose autoradiography literature, in which high-magnitude hypermetabolism was also most robustly detected in the GPe.
    Acta Neurologica Scandinavica 06/2011; 125(5):303-10. · 2.44 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the potential of 3'-deoxy-3'-[¹⁸F]fluorothymidine ([¹⁸F]FLT) positron emission tomography (PET) to detect early treatment responses in gliomas. Human glioma cells were stably transduced with genes yielding therapeutic activity, sorted for different levels of exogenous gene expression, and implanted subcutaneously into nude mice. Multimodality imaging during prodrug therapy included (a) magnetic resonance imaging, (b) PET with 9-(4-[¹⁸F]fluoro-3-hydroxymethylbutyl)guanine assessing exogenous gene expression, and (c) repeat [¹⁸F]FLT PET assessing antiproliferative therapeutic response. All stably transduced gliomas responded to therapy with significant reduction in tumor volume and [¹⁸F]FLT accumulation within 3 days after initiation of therapy. The change in [¹⁸F]FLT uptake before and after treatment correlated to volumetrically calculated growth rates. Therapeutic efficacy as monitored by [¹⁸F]FLT PET correlated to levels of therapeutic gene expression measured in vivo. Thus, [¹⁸F]FLT PET assesses early antiproliferative effects, making it a promising radiotracer for the development of novel treatments for glioma.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 06/2011; 13(3):547-57. · 2.47 Impact Factor
  • Alexander Thiel, Wolf-Dieter Heiss
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    ABSTRACT: Activated microglia is one of the most important cellular components of poststroke neuroinflammation, which occurs early in the area of the infarct but also in remote regions with fiber tract connections to the site of the primary lesion. The development of different radioligands for the translocator protein, a mitochondrial membrane protein expressed in microglial cells when they transform from the resting to the activated state, allows to study the temporal dynamics of this cellular neuroinflammatory component in vivo in animal models and human stroke using positron emission tomography. In this article, we review the advantage and limitations of current and future methods for microglia imaging as well as new results of multimodal imaging approaches in clinical stroke, which try to combine microglia imaging with diffusion tensor imaging to investigate the clinical relevance of remote microglia activation along fiber tracts for poststroke recovery.
    Stroke 02/2011; 42(2):507-12. · 6.02 Impact Factor
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    ABSTRACT: Perfusion-weighted imaging-derived maps of time-to-maximum (Tmax) are increasingly used to identify the tissue at risk in clinical stroke studies (eg, DEFUSE and EPITHET). Using quantitative positron emission tomography (PET), we evaluated Tmax to define the penumbral flow threshold in stroke patients and compared its performance to nondeconvolved time-to-peak (TTP) maps. Comparative perfusion-weighted imaging and quantitative 15O-water PET images of acute stroke patients were analyzed using cortical regions of interest. A receiver-operating characteristic curve analysis described the threshold independent performance of Tmax (area under the curve) and identified the best threshold (equal sensitivity and specificity threshold) to identify penumbral flow (< 20 mL/100 g/min on PET cerebral blood flow). The results were compared with nondeconvolved TTP and other current perfusion-weighted imaging maps using the Mann-Whitney rank-sum test. In 26 patients (time delay between MRI and PET, 65 minutes), the best threshold for penumbral flow was 5.5 seconds for Tmax (median; interquartile range, 3.9-6.6; sensitivity/specificity, 88%/89%). The area under the curve value was 0.95 (median; interquartile range, 0.93-0.97). Deconvolved Tmax did not perform significantly better than TTP (P = 0.34). Maps of Tmax detected penumbral flow but did not perform better than the easy-to-obtain maps of nondeconvolved TTP. Thus, "simple" TTP maps still remain suitable for clinical stroke studies if detailed postprocessing is not feasible.
    Stroke 10/2010; 41(12):2817-21. · 6.02 Impact Factor
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    ABSTRACT: Evidence for cholinergic dysfunction in very early stages of neurodegeneration like mild cognitive impairment (MCI) is inconclusive. Previous positron emission tomography (PET) studies based on small samples investigated if it is related to memory impairment. We examined whether cortical acetylcholine esterase (AChE) activity is reduced at this stage and correlated with cognitive function. N-[(11)C]-methyl-4-piperidyl acetate ([11C]MP4A), a positron emission tomography tracer for measuring cerebral AChE activity in vivo, was applied in 21 controls and 17 MCI patients. Parametric images of AChE activity were analyzed using standard atlas regions. Principal components analysis (PCA) of regional values of AChE activity and correlation analysis with neuropsychological test results was performed. Cortical AChE activity showed a significant decline in MCI patients compared with controls which was most pronounced in temporal regions. They formed the main part of a principal component that was related significantly to verbal and nonverbal memory, language comprehension and executive function. Cholinergic dysfunction is an early hallmark even before onset of dementia at the clinical stage of MCI. Its impact especially on temporal neocortex is associated with impaired neuropsychological function.
    Neurobiology of aging 10/2010; 33(5):867-77. · 5.94 Impact Factor
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    ABSTRACT: Perfusion-weighted (PW) MRI is increasingly used to identify the tissue at risk. The adequate PW-MRI map and threshold remain controversial due to a considerable individual variation of values. By comparative positron emission tomography, we evaluated a simple MR-based and positron emission tomography-validated calibration of PW maps. PW-MRI and quantitative positron emission tomography (15O-water) of patients with acute stroke were used to calculate averaged as well as individual thresholds of penumbral flow (positron emission tomography cerebral blood flow (<20 mL/100 g/min) for maps of time to peak, mean transit time, cerebral blood flow, and cerebral blood volume. A linear regression analysis studied the variability of the individual thresholds using 3 different PW reference regions (hemispheric, white matter, gray matter). The best model was used for volumetric analysis to compare averaged and scaled individual thresholds and to calculate look-up tables for PW maps. In 26 patients, the averaged thresholds were (median/interquartile range): cerebral blood flow 21.7 mL/100 g/min (19.9 to 32); cerebral blood volume 1.5 mL/100 g (0.9 to 1.8); mean transit time seconds 5.2 (3.9 to 6.9); and relative time to peak 4.2 seconds (2.8 to 5.8). The large individual variability was best explained by the mean value of the hemispheric reference derived from a region of interest on a level with the basal ganglia of the unaffected hemisphere (R(2): cerebral blood flow 0.76, cerebral blood volume 0.55, mean transit time 0.83, time to peak 0.95). Hemispheric reference-corrected thresholds clearly improved the detection of penumbral flow. Look-up tables were calculated to identify the individual thresholds according to the hemispheric reference value. The individual variation of PW values, even if calculated by deconvolution, remains a major obstacle in quantitative PW imaging and can be significantly improved by a simple MR-based calibration. Easily applicable look-up tables identify the individual best threshold for each PW map to optimize mismatch detection.
    Stroke 09/2010; 41(9):1939-45. · 6.02 Impact Factor
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    ABSTRACT: The aim of the Synergium was to devise and prioritize new ways of accelerating progress in reducing the risks, effects, and consequences of stroke. Preliminary work was performed by seven working groups of stroke leaders followed by a synergium (a forum for working synergistically together) with approximately 100 additional participants. The resulting draft document had further input from contributors outside the synergium. Recommendations of the Synergium are: Basic Science, Drug Development and Technology: There is a need to develop: (1) New systems of working together to break down the prevalent 'silo' mentality; (2) New models of vertically integrated basic, clinical, and epidemiological disciplines; and (3) Efficient methods of identifying other relevant areas of science. Stroke Prevention: (1) Establish a global chronic disease prevention initiative with stroke as a major focus. (2) Recognize not only abrupt clinical stroke, but subtle subclinical stroke, the commonest type of cerebrovascular disease, leading to impairments of executive function. (3) Develop, implement and evaluate a population approach for stroke prevention. (4) Develop public health communication strategies using traditional and novel (eg, social media/marketing) techniques. Acute Stroke Management: Continue the establishment of stroke centers, stroke units, regional systems of emergency stroke care and telestroke networks. Brain Recovery and Rehabilitation: (1) Translate best neuroscience, including animal and human studies, into poststroke recovery research and clinical care. (2) Standardize poststroke rehabilitation based on best evidence. (3) Develop consensus on, then implementation of, standardized clinical and surrogate assessments. (4) Carry out rigorous clinical research to advance stroke recovery. Into the 21st Century: Web, Technology and Communications: (1) Work toward global unrestricted access to stroke-related information. (2) Build centralized electronic archives and registries. Foster Cooperation Among Stakeholders (large stroke organizations, nongovernmental organizations, governments, patient organizations and industry) to enhance stroke care. Educate and energize professionals, patients, the public and policy makers by using a 'Brain Health' concept that enables promotion of preventive measures. To accelerate progress in stroke, we must reach beyond the current status scientifically, conceptually, and pragmatically. Advances can be made not only by doing, but ceasing to do. Significant savings in time, money, and effort could result from discontinuing practices driven by unsubstantiated opinion, unproven approaches, and financial gain. Systematic integration of knowledge into programs coupled with careful evaluation can speed the pace of progress.
    International Journal of Stroke 08/2010; 5(4):238-56. · 4.03 Impact Factor
  • Wolf-Dieter Heiss
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    ABSTRACT: The 'penumbra' is a concept coined in animal experiments suggesting that functionally impaired tissue can survive and recover if sufficient reperfusion is re-established within a limited time period, which depends on the level of residual flow. In an ischaemic territory, irreversible damage progresses over time from the centre of the most severe flow reduction to the periphery with less disturbed perfusion. This centrifugal progression of irreversible tissue damage is characterised by a complex cascade of interconnected electrophysiological, molecular, metabolic and perfusion disturbances. Waves of depolarisations, the peri infarct spreading depressions, inducing activation of ion pumps and liberation of excitatory transmitters play an important role in the drastically increased metabolic demand during reduced oxygen supply causing hypoxic tissue changes and lactacidosis, which further damage the tissue. Positron emission tomography allows the quantification of regional cerebral blood flow, the regional metabolic rate for oxygen and the regional oxygen extraction fraction, which can be used to identify regions with a critical reduction in these physiologic variables as indicators of penumbra and irreversible damage within ischaemic territories in animal models and patients with stroke. These positron emission tomography methods require arterial blood sampling and due to the complex logistics involved, are limited for routine application. Therefore, newer tracers were developed for the noninvasive detection of irreversible tissue damage (flumazenil) and of hypoxic tissue changes (fluoromisonidazole). As a widely applicable clinical tool, diffusion/perfusion-weighted magnetic resonance imaging is used; the 'mismatch' between perfusion and diffusion changes serves as a surrogate marker of the penumbra. However, in comparative studies of magnetic resonance imaging and positron emission tomography, diffusion-weighted imaging showed a high false-positive rate of irreversible damage, and the perfusion-weighted-diffusion-weighted mismatch overestimated the penumbra as defined by positron emission tomography. Advanced analytical procedures of magnetic resonance imaging data may improve the reliability of these surrogate markers but should be validated with quantitative procedures.
    International Journal of Stroke 08/2010; 5(4):290-5. · 4.03 Impact Factor
  • Alzheimer's and Dementia 07/2010; 6(4):S31–S32. · 17.47 Impact Factor
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    Stroke 05/2010; · 6.02 Impact Factor
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    ABSTRACT: Perfusion-weighted imaging maps are used to identify hypoperfusion in acute ischemic stroke. We evaluated maps of cerebral blood flow (CBF), cerebral blood volume, mean transit time, and time to peak (TTP) in acute stroke by comparison with positron emission tomography. Perfusion-weighted imaging and positron emission tomography were performed in 26 patients with acute ischemic stroke (median 18.5 hours after stroke onset, 65 minutes between MRI and positron emission tomography). The perfusion-weighted imaging-derived maps of CBF, cerebral blood volume, mean transit time, and TTP delay were compared with quantitative positron emission tomography CBF. A receiver-operating characteristic curve analysis identified the best perfusion-weighted imaging map and threshold to identify hypoperfusion <20 mL/100 g/min, a widely used measure of penumbral flow. Individual regression analysis of positron emission tomography CBF and perfusion-weighted imaging values were strong for CBF and TTP delay and weaker for mean transit time and cerebral blood volume, but the pooled analysis showed a large variance. Receiver-operating characteristic curve analysis identified TTP and CBF maps as most predictive (median area under the curve=0.94 and 0.93). Penumbral flow thresholds were <21.7 mL/100 g/min (CBF), <1.5 mL/100 g (cerebral blood volume), >5.3 seconds (mean transit time), and >4.2 seconds (TTP). TTP and CBF maps reached sensitivity/specificity values of 91%/82% and 89%/87%. In our sample, maps of CBF, TTP, and mean transit time yielded a good estimate of penumbral flow. The performance of TTP maps was equivalent to deconvolution techniques using an arterial input function. For all maps, the application of a predefined threshold is mandatory and calibration studies will enhance their use in acute stroke therapy as well as in clinical stroke trials.
    Stroke 03/2010; 41(3):443-9. · 6.02 Impact Factor

Publication Stats

4k Citations
541.26 Total Impact Points


  • 2013
    • Cornell University
      Ithaca, New York, United States
  • 1986–2013
    • Max Planck Institute for Metabolism Research
      Köln, North Rhine-Westphalia, Germany
  • 2012
    • Max Planck Institute for Ornithology
      • Max Planck Institute for Ornithology (Radolfzell)
      München, Bavaria, Germany
  • 2011
    • McGill University
      • Department of Neurology and Neurosurgery
      Montréal, Quebec, Canada
  • 2010
    • The University of Western Ontario
      London, Ontario, Canada
  • 1997–2010
    • University of Cologne
      • • Department of Neurology
      • • Department of Psychosomatic Medicine and Psychotherapy
      Köln, North Rhine-Westphalia, Germany
  • 2000
    • Bielefeld University
      • Physiologische Psychologie
      Bielefeld, North Rhine-Westphalia, Germany