Striatal Infarction Elicits Secondary Extrafocal MRI Changes in Ipsilateral Substantia Nigra

Focal ischemia may induce pathological alterations in brain areas distant from the primary lesion. In animal models, exofocal neuron death in the ipsilateral midbrain has been described after occlusion of the middle cerebral artery (MCA). Using sequential magnetic resonance imaging (T2- and diffusion- weighted) at 3 Tesla, we investigated acute ischemic stroke patients on days 1, 2, 6, 8, and 10 after stroke onset. Sixteen consecutive patients who had suffered a stroke involving the caudate nucleus and/or putamen of either hemisphere were recruited into the study. Four additional patients with strokes sparing the caudate nucleus and putamen but encompassing at least one- third of the MCA territory served as controls. Ischemic lesions involving striatal structures resulted in hyperintense lesions in ipsilateral midbrain that emerged between days 6 and 10 after stroke and were not present on the initial scans. In contrast, none of the control stroke patients developed secondary midbrain lesions. Hyperintense lesions in the pyramidal tract or the brain stem caused by degeneration of the corticospinal tract could be clearly distinguished from these secondary midbrain gray matter lesions and were detectable from day 2 after ischemia. Co-registration of high-resolution images with a digitized anatomic atlas revealed localization of secondary lesions primarily in the substantia nigra pars compacta. Apparent diffusion coefficient (ADC) values in the secondary lesions showed a delayed sharp decline through day 10. Normalization of ADC values was observed at late measurements. Taken together, our study demonstrates that striatal infarction elicits delayed degenerative changes in ipsilateral substantia nigra pars compacta

Automated real-time text messaging as a means for rapidly identifying acute stroke patients for clinical trials

Background Recruiting stroke patients into acute treatment trials is challenging because of the urgency of clinical diagnosis, treatment, and trial inclusion. Automated alerts that identify emergency patients promptly may improve trial performance. The main purposes of this project were to develop an automated real-time text messaging system to immediately inform physicians of patients with suspected stroke and to test its feasibility in the emergency setting. Methods An electronic standardized stroke algorithm (SSA) was implemented in the clinical information system (CIS) and linked to a remote data capture system. Within 10 minutes following the documentation and storage of basic information to CIS, a text message was triggered for patients with suspected stroke and sent to a dedicated trial physician. Each text message provided anonymized information on the exact department and unit, date and time of admission, age, sex, and National Institute of Health Stroke Scale (NIHSS) of the patient. All necessary information needed to generate a text message was already available – routine processes in the emergency department were not affected by the automated real-time text messaging system. The system was tested for three 4-week periods. Feasibility was analyzed based on the number of patients correctly identified by the SSA and the door-to-message time. Results In total, 513 text messages were generated for patients with suspected stroke (median age 74 years (19–106); 50.3% female; median NIHSS 4 (0–41)), representing 96.6% of all cases. For 48.3% of these text messages, basic documentation was completed within less than 1 hour and a text message was sent within 60 minutes after patient admission. Conclusions The system proved to be stable in generating text messages using IT-based CIS to identify acute stroke trial patients. The system operated on information which is documented routinely and did not result in a higher workload. Delays between patient admission and the text message were caused by delayed completion of basic documentation. To use the automated real-time text messaging system to immediately identify emergency patients suitable for acute stroke trials, further development needs to focus on eliminating delays in documentation for the SSA in the emergency department

High‐resolution diffusion‐weighted imaging identifies ischemic lesions in a majority of transient ischemic attack patients

Transient ischemic attack (TIA) is defined as focal neurological deficit caused by ischemia resolving within 24 hours. In a secondary analysis of a large monocentric cohort of 446 TIA patients, we explored the frequency and determinants of diffusion-weighted imaging (DWI) lesions on high-resolution magnetic resonance imaging. Overall, 240 (54%) of all TIA patients presented with DWI lesions. These patients had higher National Institute of Health Stroke Scale and ABCD2 scores and presented more frequently with vessel occlusion and perfusion deficits, but had similar functional outcome at 3 months. Taken together, high-resolution DWI provides evidence of ischemic brain injury in the majority of TIA patients. ANN NEUROL 201

Prospective study on the mismatch concept in acute stroke patients within the first 24 h after symptom onset - 1000Plus study

<p>Abstract</p> <p>Background</p> <p>The mismatch between diffusion weighted imaging (DWI) lesion and perfusion imaging (PI) deficit volumes has been used as a surrogate of ischemic penumbra. This pathophysiology-orientated patient selection criterion for acute stroke treatment may have the potential to replace a fixed time window. Two recent trials - DEFUSE and EPITHET - investigated the mismatch concept in a multicenter prospective approach. Both studies randomized highly selected patients (n = 74/n = 100) and therefore confirmation in a large consecutive cohort is desirable. We here present a single-center approach with a 3T MR tomograph next door to the stroke unit, serving as a bridge from the ER to the stroke unit to screen all TIA and stroke patients. Our primary hypothesis is that the prognostic value of the mismatch concept is depending on the vessel status. Primary endpoint of the study is infarct growth determined by imaging, secondary endpoints are neurological deficit on day 5-7 and functional outcome after 3 months.</p> <p>Methods and design</p> <p>1000Plus is a prospective, single centre observational study with 1200 patients to be recruited. All patients admitted to the ER with the clinical diagnosis of an acute cerebrovascular event within 24 hours after symptom onset are screened. Examinations are performed on day 1, 2 and 5-7 with neurological examination including National Institute of Health Stroke Scale (NIHSS) scoring and stroke MRI including T2*, DWI, TOF-MRA, FLAIR and PI. PI is conducted as dynamic susceptibility-enhanced contrast imaging with a fixed dosage of 5 ml 1 M Gadobutrol. For post-processing of PI, mean transit time (MTT) parametric images are determined by deconvolution of the arterial input function (AIF) which is automatically identified. Lesion volumes and mismatch are measured and calculated by using the perfusion mismatch analyzer (PMA) software from ASIST-Japan. Primary endpoint is the change of infarct size between baseline examination and day 5-7 follow up.</p> <p>Discussions</p> <p>The aim of this study is to describe the incidence of mismatch and the predictive value of PI for final lesion size and functional outcome depending on delay of imaging and vascular recanalization. It is crucial to standardize PI for future randomized clinical trials as for individual therapeutic decisions and we expect to contribute to this challenging task.</p> <p>Trial Registration</p> <p>clinicaltrials.gov NCT00715533</p

Reduction of Measurement Uncertainty in Magnetic Resonance Perfusion Imaging

Perfusionsmessungen des Gehirns mittels Magnetresonanztomographie (MRT) werden im Wesentlichen mit Bolus-Track-Techniken durchgeführt. Der bisherige Ansatz hat zwei relevante Limitationen: i) Bei wiederholten Messungen am gleichen Individuum zeigen die Perfusionsparameter eine hohe Varianz und erschweren somit longitudinale Studien. ii) Die Perfusionskarten sind bislang nur unzureichend quantifizierbar, wobei im Fall einer eingeschränkten Blut-Hirn- Schranke ein besonderes Fehlerpotential vorliegt. Es wurde daher die Hypothese verfolgt, dass der Einfluss beider Faktoren durch die Anwendung zweier Postprocessing-Strategien begrenzt werden kann. Zur Überwindung dieser beiden Limitationen wurde eine verbesserte Nachverarbeitung der MRT-Daten entwickelt: i) Zur Reduktion der Varianz der Perfusionsparameter dient ein neuer Algorithmus zur Korrektur von Sättigungseffekten in der Arteriellen Inputfunktion. ii) Um eine Bestimmung der Perfusionsparameter auch bei gestörter Blut-Hirn-Schranke zu ermöglichen, wurde ein bereits publiziertes Verfahren als Software implementiert. Beide Verfahrensverbesserungen wurden in klinischen Studien angewandt bzw. evaluiert und in einem Fall auch in einer Computersimulation getestet. Schließlich wird ein Ausblick auf ein neues Konzept zur Absolutquantifizierung durch Integration individueller angiographischer Daten gegeben. Die Methode zur Varianzreduktion mittels verbesserter Darstellung der arteriellen Inputfunktion erwies sich in Monte- Carlo-Simulationen als robust. Insbesondere konnte gezeigt werden, dass sich damit die Bolus-Track-Bildgebung auch bei geringem Signal-Rausch-Verhältnis oder hohen Kontrastmitteldosierungen anwenden lässt. Die Ergebnisse einer Humanstudie (n = 21) mit wiederholten Messungen am gleichen Individuum belegten ferner, dass diese Methode die Sensitivität und Reproduzierbarkeit einer Messung erhöhen kann und somit im Ausblick die Möglichkeit bietet, neue Formen longitudinaler Studien zu betreiben. In einem anderen Anwendungsfeld wurden bei Patienten mit Multipler Sklerose trotz bestehender Extravasation des Kontrastmittels longitudinale Perfusionsveränderungen mit der MRT quantifiziert. Diese Technik fand weiter in einer Studie zur Sicherheit der kontrastmittelbasierten Ultraschallbildgebung Anwendung. Erste Resultate an in-vivo-Daten weisen ferner auf die potentielle Nutzbarkeit der individuellen Gefäßgeometrie zur Quantifizierung der Bolus-Track-Technik hin.Clinical perfusion measurements of the brain were usually performed utilizing dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI). However, this approach has two severe limitations: i) Repeated measurements of the same subject show large variations in the calculated parameter maps which is a disadvantage for longitudinal studies. ii) Quantification of parameter maps is currently limited, especially in the case of a disrupted blood-brain barrier. This was motivation enough to overcome both limitations and led to the hypothesis, that two different post-processing algorithms would be able to do that: i) In order to limit variations in perfusion parameter maps, a novel algorithm was developed which is able to deal with saturation effects in the arterial input function (AIF). ii) In order to estimate perfusion parameters also in case of a disrupted blood-brain barrier, an already published algorithm was implemented as a software program. Both methods were evaluated in clinical studies, and for the saturation correction also in a Monte Carlo simulation. Finally, as an outlook, a novel concept of absolute perfusion quantification by involving angiographic techniques is presented. In the Monte Carlo simulation the algorithm correcting the saturation effects was evaluated as robust and effective. Especially, this approach allows DSC-MRI also in case of low signal-to-noise ratios as well as for high dosages of the contrast agent. A human study (n = 21) with repeated measurements of the same subjects has further proven that this method is able to improve sensitivity and reproducibility in perfusion imaging, and enabling therefore new forms of longitudinal studies. In another topic of research perfusion changes in patients with multiple sclerosis were quantified longitudinally despite of an leaking blood-brain barrier. The same technique was also applied in a safety study on diagnostic ultrasound imaging. Finally, first in-vivo results combining DSC-MRI and MR angiography show the potential usability of this approach for absolute quantification in perfusion imaging

Automated vs manual delineations of regions of interest- a comparison in commercially available perfusion MRI software

Abstract Background In perfusion magnetic resonance imaging a manual approach to delineation of regions of interest is, due to rater bias and time intensive operator input, clinically less favorable than an automated approach would be. The goal of our study was to compare the performances of these approaches. Methods Using Stroketool, PMA and Perfscape/Neuroscape perfusion maps of cerebral blood flow, mean transit time and Tmax were created for 145 patients with acute ischemic stroke. Volumes of hypoperfused tissue were calculated using both a manual and an automated protocol, and the results compared between methods. Results The median difference between the automatically and manually derived volumes was up to 210 ml in Perfscape/Neuroscape, 123 ml in PMA and 135 ml in Stroketool. Correlation coefficients between perfusion volumes and radiological and clinical outcome were much lower for the automatic volumes than for the manually derived ones. Conclusions The agreement of the two methods was very poor, with the automated use producing falsely exaggerated volumes of hypoperfused tissue. Software improvements are necessary to enable highly automated protocols to credibly assess perfusion deficits.</p

Preserved Responsiveness of Secondary Somatosensory Cortex in Patients with Thalamic Stroke

Cortical representations may change when somatosensory input is altered. Here, we investigated the functional consequences of partial ‘‘central’ ’ deafferentation of the somatosensory cortex due to a lesion of the ventroposterior lateral nucleus (VPL) in patients at a chronic stage after solitary infarction of the thalamus. Event-related functional magnetic resonance imaging during electrical index finger stimulation of the affected and nonaffected side was performed in 6 patients exhibiting contralesional sensory deficits (mainly hypesthesia). Involvement of the VPL and additional nuclei was determined by high-resolution magnetic resonance imaging (MRI) and subsequent MRI-to-atlas coregistration. For the group, statistical parametric maps showed a reduced activation of contralateral primary somatosensory cortex (SI) in response to stimulation of the affected side. However, no significant difference in the activation of contralateral secondary somatosensory cortex (SII) compared with stimulation of the nonaffected side was detected. Correspondingly, the ratio of SII-to-SI activation for the ipsilesional hemisphere was markedly elevated as compared with the contralesional hemisphere. For preserved responsiveness of SII in thalamic stroke comparable with that of the contralesional hemisphere, possible explanations are a direct thalamocortical input to SII mediating parallel information processing, nonlinear response behavior of SII in serial processing, or reorganizational processes that evolved over time

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Automated real-time text messaging as a means for rapidly identifying acute stroke patients for clinical trial