Connectivity Concordance Mapping: A New Tool for Model-Free Analysis of fMRI Data of the Human Brain

Functional magnetic resonance data acquired in a task-absent condition (“resting state”) require new data analysis techniques that do not depend on an activation model. Here, we propose a new analysis method called Connectivity Concordance Mapping (CCM). The main idea is to assign a label to each voxel based on the reproducibility of its whole-brain pattern of connectivity. Specifically, we compute the correlations of time courses of each voxel with every other voxel for each measurement. Voxels whose correlation pattern is consistent across measurements receive high values. The result of a CCM analysis is thus a voxel-wise map of concordance values. Regions of high inter-subject concordance can be assumed to be functionally consistent, and may thus be of specific interest for further analysis. Here we present two fMRI studies to demonstrate the possible applications of the algorithm. The first is a eyes-open/eyes-closed paradigm designed to highlight the potential of the method in a relatively simple domain. The second study is a longitudinal repeated measurement of a patient following stroke. Longitudinal clinical studies such as this may represent the most interesting domain of applications for this algorithm

results of the sifap1 study

Objectives The present study aimed to evaluate the frequency of warning signs in younger patients with stroke with a special regard to the ‘FAST’ scheme, a public stroke recognition instrument (face, arm, speech, timely). Setting Primary stroke care in participating centres of a multinational European prospective cross-sectional study (Stroke in Young Fabry Patients; sifap1). Forty-seven centres from 15 European countries participate in sifap1. Participants 5023 acute patients with stroke (aged 18–55 years) patients (96.5% Caucasians) were enrolled in the study between April 2007 and January 2010. Primary and secondary outcome measures sifap1 was originally designed to investigate the relation of juvenile stroke and Fabry disease. A secondary aim of sifap1 was to investigate stroke patterns in this specific group of patients. The present investigation is a secondary analysis addressing stroke presenting symptoms with a special regard to signs included in the FAST scheme. Results 4535 patients with transient ischaemic attack (TIA; n=1071), ischaemic stroke (n=3396) or other (n=68) were considered in the presented analysis. FAST symptoms could be traced in 76.5% of all cases. 35% of those with at least one FAST symptom had all three symptoms. At least one FAST symptom could be recognised in 69.1% of 18–24 years-old patients, in 74% of those aged 25–34 years, in 75.4% of those aged 35–44 years, and 77.8% in 45–55 years-old patients. With increasing stroke severity signs included in the FAST scheme were more prevalent (National Institute of Health Stroke Scale, NIHSS15: 100%). Clustering clinical signs according to FAST lower percentages of strokes in the posterior circulation (65.2%) and in patients with TIA (62.3%) were identified. Conclusions FAST may be applied as a useful and rapid tool to identify stroke symptoms in young individuals aged 18–55 years. Especially in patients eligible for thrombolysis FAST might address the majority of individuals

Clinically relevant depressive symptoms in young stroke patients - results of the sifap1 study

BACKGROUND Although post-stroke depression is widely recognized, less is known about depressive symptoms in the acute stage of stroke and especially in young stroke patients. We thus investigated depressive symptoms and their determinants in such a cohort. METHODS The Stroke in Young Fabry Patients study (sifap1) prospectively recruited a large multinational European cohort (n = 5,023) of patients with a cerebrovascular event aged 18-55. For assessing clinically relevant depressive symptoms (CRDS, defined by a BDI-score ≥18) the self-reporting Beck Depression Inventory (BDI) was obtained on inclusion in the study. Associations with baseline parameters, stroke severity (National Institutes of Health Stroke Scale, NIHSS), and brain MRI findings were analyzed. RESULTS From the 2007 patients with BDI documentation, 202 (10.1%) had CRDS. CRDS were observed more frequently in women (12.6 vs. 8.2% in men, p < 0.001). Patients with CRDS more often had arterial hypertension, diabetes mellitus, and hyperlipidemia than patients without CRDS (hypertension: 58.0 vs. 47.1%, p = 0.017; diabetes mellitus: 17.9 vs. 8.9%, p < 0.001; hyperlipidemia: 40.5 vs. 32.3%, p = 0.012). In the subgroup of patients with ischemic stroke or TIA (n = 1,832) no significant associations between CRDS and cerebral MRI findings such as the presence of acute infarcts (68.1 vs. 65.8%, p = 0.666), old infarctions (63.4 vs. 62.1%, p = 0.725) or white matter hyper-intensities (51.6 vs. 53.7%, p = 0.520) were found. CONCLUSION Depressive symptoms were present in 10.1% of young stroke patients in the acute phase, and were related to risk factors but not to imaging findings

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

Pre- and inhospital management of patients with acute stroke

In der vorliegenden kumulativen Habilitationsschrift werden Arbeiten zur prä‐ und intrahospitalen Versorgung von Patienten mit akutem Schlaganfall vorgestellt und diskutiert. In einer großen bevölkerungsbasierten Befragung wurde durch die Kombination einer Frage nach vorherigem Schlaganfall mit Fragen nach bestimmten Schlaganfallsymptomen die Prävalenz von Schlaganfall‐Erkrankungen in verschiedenen Altersgruppen erfasst. Eine höhere Prävalenz war assoziiert mit Faktoren wie höherem Lebensalter, männlichem Geschlecht, nicht‐deutscher Nationalität, niedrigerem Bildungsstand, Schlaganfall in der Familie oder alleine zu leben. In der gleichen Befragung von mehr als 75.000 Haushalten im Berliner Innenstadtraum wurde ein relativ niedriger Kenntnisstand von Risikofaktoren für Schlaganfall erfasst. Genannte Informationsquellen zum Schlaganfall variierten entsprechend unterschiedlicher Populationscharakteristika. Im Rahmen der prospektiven Berliner Schlaganfallstudie (BASS) wurden die Zeitintervalle sowie Faktoren der prä‐ und der intrahospitalen Versorgung untersucht. Hierbei wurden bei verschiedenen Gruppen deutliche Unterschiede bzw. Verzögerungen im Zeitintervall von Symptombeginn bis zur Aufnahme im Krankenhaus (prähospitale Zeit) und von Aufnahme bis zur Durchführung der zerebralen Bildgebung (intrahospital) beobachtet. Diese Verzögerungen wurden prähospital durch Faktoren wie die Art des Transports in die Klinik, die Dauer bzw. Persistenz der Symptome, Alter der Patienten und durch bestimmte Verhaltensmuster von Patienten und Angehörigen, intrahospital durch die vorhergehende prähospitale Zeit, die Versorgung am jeweiligen Krankenhaus und durch den Wochentag und schließlich prä‐ und intrahospital wesentlich durch die Schwere des Schlaganfalls beeinflusst. Programme und Maßnahmen zur Verbesserung der prä‐ und der intrahospitalen Versorgung müssen darauf zielen, die Aufmerksamkeit für den Schlaganfall und seiner Symptome weiter zu erhöhen sowie anhand von Qualitätskriterien die Einhaltung von Standards in der akuten Versorgungskette zu fördern. Die in der Regel wichtigsten diagnostischen Maßnahmen zur Planung von Akuttherapie und Sekundärprophylaxe sind die zerebrale Schnittbildgebung und die Gefäßdiagnostik im Rahmen von CT und MRT oder durch Ultraschall. Bei Patienten mit einer klinischen TIA (nach WHO‐Definition) kann ein höherer Wert im ABCD2 TIA‐Risiko‐Score darauf hinweisen, dass sich Nachweise eines strukturellen Gewebeinfarkts in der diffusionsgewichteten MRT finden. Eine sichere Differenzierung zwischen klinischer TIA und Infarkt mittels ABCD2‐Score erscheint dagegen nicht möglich. Bei Patienten mit zerebraler Mikroangiopathie fanden sich nach Anwendung kontrastmittel‐unterstützter farbkodierter transkranieller Duplexsonographie (TCCS) keine Nachweise einer Störung der Bluthirnschranke im MRT. Dies ist ein weiteres Argument für die Sicherheit dieser einfachen und schnell‐anwendbaren nicht‐invasiven Untersuchungsmethode. Die Wahl der diagnostischen Mittel beim akuten Schlaganfall definiert sich aus den individuellen klinischen Notwendigkeiten und aus den verfügbaren Ressourcen. Schwerpunkte zukünftiger klinischer Forschung werden eine intensivierte Prävention, die interventionelle und die Behandlung von Patienten mit Aufwach‐Schlaganfällen sowie die Therapie von Komplikationen nach Schlaganfall sein. Die Bildung neurovaskulärer Zentren zur Forschung und zur Behandlung wird dabei von zunehmender Bedeutung sein.In this cumulative paper (Habilitationsschrift) publications of the authors concerning the pre- and inhospital management of patients with acute stroke are discussed. First a paper evaluating the prevalence of stroke is presented. Factors influenceing and reasons causing delays in pre- and inhospital management are presented. Aspects of inhospital diagnostic workup of acute stroke patients are discussed