Oral anticoagulation in patients with atrial fibrillation and acute ischaemic stroke: design and baseline data of the prospective multicentre Berlin Atrial Fibrillation Registry.

AIMS: The Berlin Atrial Fibrillation Registry was designed to analyse oral anticoagulation (OAC) prescription in patients with atrial fibrillation (AF) and acute ischaemic stroke. METHODS AND RESULTS: This investigator-initiated prospective multicentre registry enrolled patients at all 16 stroke units located in Berlin, Germany. The ongoing telephone follow-up is conducted centrally and will cover 5 years per patient. Within 2014 and 2016, 1080 patients gave written informed consent and 1048 patients were available for analysis. Median age was 77 years [interquartile range (IQR) 72-83], 503 (48%) patients were female, and 254 (24%) had a transient ischaemic attack (TIA). Overall, 470 (62%) out of 757 patients with known AF and a (pre-stroke) CHA2DS2-VASc ≥ 1 were anticoagulated at the time of stroke. At hospital discharge, 847 (81.3%) of 1042 patients were anticoagulated. Thereof 710 (68.1%) received a non-vitamin K-dependent oral anticoagulant (NOAC) and 137 (13.1%) a vitamin K antagonist (VKA). Pre-stroke intake of a NOAC [odds ratio (OR) 15.6 (95% confidence interval, 95% CI 1.97-122)] or VKA [OR 0.04 (95% CI 0.02-0.09)], an index TIA [OR 0.56 (95% CI 0.34-0.94)] rather than stroke, heart failure [OR 0.49 (95% CI 0.26-0.93)], and endovascular thrombectomy at hospital admission [OR 12.9 (95% CI 1.59-104)] were associated with NOAC prescription at discharge. Patients' age or AF type had no impact on OAC or NOAC use, respectively. CONCLUSION: About 60% of all registry patients with known AF received OAC at the time of stroke or TIA. At hospital discharge, more than 80% of AF patients were anticoagulated and about 80% of those were prescribed a NOAC.

MRI Brain Changes After Marathon Running: Results of the Berlin Beat of Running Study.

Several studies report neurological complications such as brain injury induced by ischemia or edema following exhaustive endurance sport. We aimed to detect the frequency of acute brain lesions after a marathon race. In the prospective observational Berlin Beat of Running study, 110 experienced endurance athletes underwent 3-Tesla brain MRI exams 2-3 days prior and within 2 days after a marathon run. MRI results were compared to an age- and sex-matched control group of 68 non-athletes, including the "Age-Related White Matter Changes" (ARWMC) scale to assess white matter lesions (WML) in the brain. 108 athletes (median age 48 years, 24% female, 8% with hypertension; 0% with diabetes) completed the race. No athlete reported neurological deficits, but a single acute ischemic lesion was detected in diffusion-weighted MRI after the race in one athlete. No other acute brain lesions compared to prior MRI were found. An ARWMC score ≥4 was found in 15% of athletes and 12% of non-athletic controls (p=0.7). Chronic ischemic lesions were not found in athletes but in four controls (6%) (p=0.02). In conclusion, acute ischemic brain lesions may be found in endurance runners. Every seventh endurance athlete and every ninth control showed evidence for substantial white matter lesions.

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.

Kidney function and white matter disease in young stroke patients: analysis of the stroke in young fabry patients study population.

BACKGROUND AND PURPOSE: Impaired kidney function is thought to be associated with small vessel disease, outcome, and mortality in the general stroke population. Data are limited regarding young patients. The aim of this study was to investigate the association of kidney function and white matter hyperintensities (WMHs) in young patients with first ischemic stroke. METHODS: We analyzed 2500 young (18-55 years) patients with first-ever ischemic stroke from the prospective observational Stroke in Young Fabry Patients (SIFAP1) study with available MRI data on WMH. Of these, 2009 had available data concerning estimated glomerular filtration rate (eGFR). Kidney function was expressed as eGFR by the Modification of Diet in Renal Disease method. Deep WMHs on MRI were classified by the Fazekas score. Multivariate analysis was performed using a regression model with random effects. RESULTS: Mean eGFR was 96.7 mL/min in those with WMH Grade 0 to 1 (none to mild), 90.7 mL/min in WMH Grade 2 (moderate), and 89 mL/min in WMH Grade 3 (severe). Univariate analysis revealed WMH to be associated with age (P<0.001), hypertension (P<0.001), cardiovascular disease (P=0.015), overweight (body mass index >25 kg/m(2); P=0.013), current smoking (P=0.044), and eGFR (P=0.009). In multivariate analysis, age, hypertension, and eGFR remained associated with WMH severity. CONCLUSIONS: In young patients with acute ischemic stroke, lower eGFR values in the normal range are associated with the presence of moderate to severe WMH. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00414583.

Rate of cardiac arrhythmias and silent brain lesions in experienced marathon runners: rationale, design and baseline data of the Berlin Beat of Running study.

BACKGROUND: Regular exercise is beneficial for cardiovascular health but a recent meta-analysis indicated a relationship between extensive endurance sport and a higher risk of atrial fibrillation, an independent risk factor for stroke. However, data on the frequency of cardiac arrhythmias or (clinically silent) brain lesions during and after marathon running are missing. METHODS/DESIGN: In the prospective observational "Berlin Beat of Running" study experienced endurance athletes underwent clinical examination (CE), 3 Tesla brain magnetic resonance imaging (MRI), carotid ultrasound imaging (CUI) and serial blood sampling (BS) within 2-3 days prior (CE, MRI, CUI, BS), directly after (CE, BS) and within 2 days after (CE, MRI, BS) the 38th BMW BERLIN-MARATHON 2011. All participants wore a portable electrocardiogram (ECG)-recorder throughout the 4 to 5 days baseline study period. Participants with pathological MRI findings after the marathon, troponin elevations or detected cardiac arrhythmias will be asked to undergo cardiac MRI to rule out structural abnormalities. A follow-up is scheduled after one year. RESULTS: Here we report the baseline data of the enrolled 110 athletes aged 36-61 years. Their mean age was 48.8 ± 6.0 years, 24.5% were female, 8.2% had hypertension and 2.7% had hyperlipidaemia. Participants have attended a mean of 7.5 ± 6.6 marathon races within the last 5 years and a mean of 16 ± 36 marathon races in total. Their weekly running distance prior to the 38th BMW BERLIN-MARATHON was 65 ± 17 km. Finally, 108 (98.2%) Berlin Beat-Study participants successfully completed the 38th BMW BERLIN-MARATHON 2011. DISCUSSION: Findings from the "Berlin Beats of Running" study will help to balance the benefits and risks of extensive endurance sport. ECG-recording during the marathon might contribute to identify athletes at risk for cardiovascular events. MRI results will give new insights into the link between physical stress and brain damage. TRIAL REGISTRATION: clinicaltrials.gov NCT01428778.

Off-label-dosing of non-vitamin K-dependent oral antagonists in AF patients before and after stroke: results of the prospective multicenter Berlin Atrial Fibrillation Registry.

AIMS: We aimed to analyze prevalence and predictors of NOAC off-label under-dosing in AF patients before and after the index stroke. METHODS: The post hoc analysis included 1080 patients of the investigator-initiated, multicenter prospective Berlin Atrial Fibrillation Registry, designed to analyze medical stroke prevention in AF patients after acute ischemic stroke. RESULTS: At stroke onset, an off-label daily dose was prescribed in 61 (25.5%) of 239 NOAC patients with known AF and CHA2DS2-VASc score ≥ 1, of which 52 (21.8%) patients were under-dosed. Under-dosing was associated with age ≥ 80 years in patients on rivaroxaban [OR 2.90, 95% CI 1.05-7.9, P = 0.04; n = 29] or apixaban [OR 3.24, 95% CI 1.04-10.1, P = 0.04; n = 22]. At hospital discharge after the index stroke, NOAC off-label dose on admission was continued in 30 (49.2%) of 61 patients. Overall, 79 (13.7%) of 708 patients prescribed a NOAC at hospital discharge received an off-label dose, of whom 75 (10.6%) patients were under-dosed. Rivaroxaban under-dosing at discharge was associated with age ≥ 80 years [OR 3.49, 95% CI 1.24-9.84, P = 0.02; n = 19]; apixaban under-dosing with body weight ≤ 60 kg [OR 0.06, 95% CI 0.01-0.47, P < 0.01; n = 56], CHA2DS2-VASc score [OR per point 1.47, 95% CI 1.08-2.00, P = 0.01], and HAS-BLED score [OR per point 1.91, 95% CI 1.28-2.84, P < 0.01]. CONCLUSION: At stroke onset, off-label dosing was present in one out of four, and under-dosing in one out of five NOAC patients. Under-dosing of rivaroxaban or apixaban was related to old age. In-hospital treatment after stroke reduced off-label NOAC dosing, but one out of ten NOAC patients was under-dosed at discharge. CLINICAL TRIAL REGISTRATION: NCT02306824.

Unraveling the steroid hormone response in male marathon runners: Correlation of running time with aldosterone and progesterone.

Marathon running is a physical and psychological stressor. We aimed to characterize the response of nine steroid hormones, which include estradiol, progesterone, testosterone, cortisol, aldosterone, 17-hydroxyprogesterone, cortisone, androstenedione, and dehydroepiandrosterone sulfate, to marathon running and their association with performance. Blood samples of sixty men (age: 49.3 ± 5.9 years) who participated in the Berlin marathon were collected within 3 days before, within 30 min and within 58 h after the end of the marathon. The nine steroid hormones in serum were quantified using liquid chromatography-tandem mass spectrometry. The responses of nine steroid hormones to marathon running were characterized. Aldosterone (fold change: 8.5), progesterone (fold change: 6.6), and cortisol (fold change: 3.7) showed significant increases within 30 min after the marathon (all p < 0.0001). Estradiol but not testosterone increased in the male runners. Marathon running time was significantly related to aldosterone increase (beta=-0.238, p = 0.008) and progesterone increase (beta=-0.192, p = 0.036) in addition to body mass index, self-reported training distance, and age. Serum progesterone correlated with aldosterone and cortisol (r = 0.81 and r = 0.92, respectively, p < 0.001). Progesterone, as a precursor hormone, is increased after the completion of marathon running in association with the increase of aldosterone and cortisol. These findings reveal a contribution of progesterone during the response to the psycho-physical stress of marathon running in males.

[Medicine and Economy: Measures for a Science Based, Patient-Centred and Resource Conscious Care. The Association of Scientific Medical Societies' (AWMF) Strategy Paper]. / Medizin und Ökonomie: Maßnahmen für eine wissenschaftlich begründete, patientenzentrierte und ressourcenbewusste Versorgung. Ein Strategiepapier der Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften (AWMF).

The AWMF and its medical societies perceive an increasing dominance of economic targets in the hospital health care sector, leading to impairment of patient care. While resource use in health care should be appropriate, efficient and fairly allocated, "economization" creates a burdensome situation for physicians, nurses and other health care professionals.The AMWF and the medical societies studied causes and developed measures for a scientific, patient-centred and resource-conscious medical care. Disincentives due to the remuneration system, number and equipment of hospitals resp. specialist departments and their basic funding need to be overcome. Proposed actions relate to the patient-doctor-level, the management level of hospitals and the level of planning and financing hospitals including compensation of hospital care. To place patients and their health in the forefront again, joint efforts of all stakeholders in health care are needed.

Correcting saturation effects of the arterial input function in dynamic susceptibility contrast-enhanced MRI: a Monte Carlo simulation.

To prevent systematic errors in quantitative brain perfusion studies using dynamic susceptibility contrast-enhanced magnetic resonance imaging (DSC-MRI), a reliable determination of the arterial input function (AIF) is essential. We propose a novel algorithm for correcting distortions of the AIF caused by saturation of the peak amplitude and discuss its relevance for longitudinal studies. The algorithm is based on the assumption that the AIF can be separated into a reliable part at low contrast agent concentrations and an unreliable part at high concentrations. This unreliable part is reconstructed, applying a theoretical framework based on a transport-diffusion theory and using the bolus-shape in the tissue. A validation of the correction scheme is tested by a Monte Carlo simulation. The input of the simulation was a wide range of perfusion, and the main aim was to compare this input to the determined perfusion parameters. Another input of the simulation was an AIF template derived from in vivo measurements. The distortions of this template was modeled via a Rician distribution for image intensities. As for a real DSC-MRI experiment, the simulation returned the AIF and the tracer concentration-dependent signal in the tissue. The novel correction scheme was tested by deriving perfusion parameters from the simulated data for the corrected and the uncorrected case. For this analysis, a common truncated singular value decomposition approach was applied. We find that the saturation effect caused by Rician-distributed noise leads to an overestimation of regional cerebral blood flow and regional cerebral blood volume, as compared to the input parameter. The aberration can be amplified by a decreasing signal-to-noise ratio (SNR) or an increasing tracer concentration. We also find that the overestimation can be successfully eliminated by the proposed saturation-correction scheme. In summary, the correction scheme will allow DSC-MRI to be expanded towards higher tracer concentrations and lower SNR and will help to increase the measurement to measurement reproducibility for longitudinal studies.

Frequency of exercise-induced ST-T-segment deviations and cardiac arrhythmias in recreational endurance athletes during a marathon race: results of the prospective observational Berlin Beat of Running study.

OBJECTIVES: While regular physical exercise has many health benefits, strenuous physical exercise may have a negative impact on cardiac function. The 'Berlin Beat of Running' study focused on feasibility and diagnostic value of continuous ECG monitoring in recreational endurance athletes during a marathon race. We hypothesised that cardiac arrhythmias and especially atrial fibrillation are frequently found in a cohort of recreational endurance athletes. The main secondary hypothesis was that pathological laboratory findings in these athletes are (in part) associated with cardiac arrhythmias. DESIGN: Prospective observational cohort study including healthy volunteers. SETTING AND PARTICIPANTS: One hundred and nine experienced marathon runners wore a portable ECG recorder during a marathon race in Berlin, Germany. Athletes underwent blood tests 2-3 days prior, directly after and 1-2 days after the race. RESULTS: Overall, 108 athletes (median 48 years (IQR 45-53), 24% women) completed the marathon in 249±43 min. Blinded ECG analysis revealed abnormal findings during the marathon in 18 (16.8%) athletes. Ten (9.3%) athletes had at least one episode of non-sustained ventricular tachycardia, one of whom had atrial fibrillation; eight (7.5%) individuals showed transient ST-T-segment deviations. Abnormal ECG findings were associated with advanced age (OR 1.11 per year, 95% CI 1.01 to 1.23), while sex and cardiovascular risk profile had no impact. Directly after the race, high-sensitive troponin T was elevated in 18 (16.7%) athletes and associated with ST-T-segment deviation (OR 9.9, 95% CI 1.9 to 51.5), while age, sex and cardiovascular risk profile had no impact. CONCLUSIONS: ECG monitoring during a marathon is feasible. Abnormal ECG findings were present in every sixth athlete. Exercise-induced transient ST-T-segment deviations were associated with elevated high-sensitive troponin T (hsTnT) values. TRIAL REGISTRATION: ClinicalTrials.gov NCT01428778; Results.

Frequency of MELAS main mutation in a phenotype-targeted young ischemic stroke patient population.

Mitochondrial diseases, predominantly mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), may occasionally underlie or coincide with ischemic stroke (IS) in young and middle-aged individuals. We searched for undiagnosed patients with MELAS in a target subpopulation of unselected young IS patients enrolled in the Stroke in Young Fabry Patients study (sifap1). Among the 3291 IS patients aged 18-55 years recruited to the sifap1 study at 47 centers across 14 European countries, we identified potential MELAS patients with the following phenotypic features: (a) diagnosed cardiomyopathy or (b) presence of two of the three following findings: migraine, short stature (≤165 cm for males; ≤155 cm for females), and diabetes. Identified patients' blood samples underwent analysis of the common MELAS mutation, m.3243A>G in the MTTL1 gene of mitochondrial DNA. Clinical and cerebral MRI features of the mutation carriers were reviewed. We analyzed blood samples of 238 patients (177 with cardiomyopathy) leading to identification of four previously unrecognized MELAS main mutation carrier-patients. Their clinical and MRI characteristics were within the expectation for common IS patients except for severe hearing loss in one patient and hyperintensity of the pulvinar thalami on T1-weighted MRI in another one. Genetic testing for the m.3243A>G MELAS mutation in young patients with IS based on phenotypes suggestive of mitochondrial disease identifies previously unrecognized carriers of MELAS main mutation, but does not prove MELAS as the putative cause.

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.

Out-of-hospital delays in patients with acute stroke.

STUDY OBJECTIVE: We determine the interval between stroke symptom onset and time to emergency department (ED) arrival and factors associated with delays in presentation. METHODS: All patients with acute stroke presenting at 4 hospitals in a metropolitan area and consenting to an interview were prospectively included over a 12-month period, excluding patients with presentation greater than 7 days after onset of symptoms and discharge or death within 24 hours after ED arrival. Initially, National Institutes of Health Stroke Scale and times of symptom onset and of ED arrival were registered by a neurologist. Sociodemographic factors and data about the course of events were obtained by standardized interview conducted with patients or proxies. In a multivariable analysis, an extended Cox proportional hazards model was used, and hazard ratios were determined. RESULTS: Primary analyses were performed for 558 interviewed patients (mean age 66.8+/-13.5 years, 45% female patients) with confirmed stroke; 452 (81%) patients had a known onset of symptoms. Median interval between symptom onset and ED arrival was 151 minutes (range 5 to 9,590 minutes). Transport by emergency medical services (adjusted hazard ratio 0.28 [95% confidence interval (CI) 0.19 to 0.41]), increasing age (hazard ratio 0.99 [95% CI 0.98 to 0.99]), greater stroke severity (National Institutes of Health Stroke Scale score; hazard ratio 0.93 [95% CI 0.90 to 0.96]), having transient ischemic attack rather than persistent symptoms (hazard ratio 0.32 [95% CI 0.22 to 0.46]) and symptoms considered urgent (hazard ratio 0.68 [95% CI 0.55 to 0.84]) were the factors most strongly associated with a shorter out-of-hospital interval. CONCLUSION: There are considerable delays between stroke symptom onset and ED arrival. Programs to improve awareness of patients with stroke to seek medical help immediately may reduce unnecessary delays to ED arrival.

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.

Should transesophageal echocardiography be performed in acute stroke patients with atrial fibrillation?

The diagnostic need for echocardiography in acute stroke patients with documented atrial fibrillation (AF) is controversial because the index stroke per se is an indication for therapeutic anticoagulation according to guidelines. We retrospectively analyzed medical records of 2390 stroke patients consecutively admitted over a 2-year period to three different stroke units at university hospitals in Berlin, Germany. AF was diagnosed in 21.2% (n=506) of 2185 patients with acute ischemic stroke or transient ischemic attack. Overall, 36.6% (n=185) of all AF patients underwent transesophageal echocardiography (TEE) or transthoracic echocardiography within days of hospital admission. According to multivariate analysis, age and in-hospital conventions determined the diagnostic use of TEE in stroke patients with known AF, while the existing cardiovascular risk profile had no impact. Major cardiac sources of embolism were identified by echocardiography in 9.7% (n=18) of all AF patients with acute stroke, including non-AF-related sources of embolism in 3.8% (n=7). However, echocardiographic findings did not result in any therapeutic intervention other than immediate anticoagulation. Furthermore, echocardiographic findings had no impact on the prescription of anticoagulants at hospital discharge or long-term survival. Taken together, our data indicate that diagnostic echocardiography offers only a little additional information and does not impact clinical management and outcome in acute stroke patients with known AF.

Longitudinal effects of lesions on functional networks after stroke.

While ischemic stroke reflects focal damage determined by the affected vascular territory, clinical symptoms are often more complex and may be better explained by additional indirect effects of the focal lesion. Assumed to be structurally underpinned by anatomical connections, supporting evidence has been found using alterations in the functional connectivity of resting-state functional magnetic resonance imaging (fMRI) data in both sensorimotor and attention networks. To assess the generalizability of this phenomenon in a stroke population with heterogeneous lesions, we investigated the distal effects of lesions on a global level. Longitudinal resting-state fMRI scans were acquired at three consecutive time points, beginning during the acute phase (days 1, 7, and 90 post-stroke) in 12 patients after ischemic stroke. We found a preferential functional change in affected networks (i.e., networks containing lesions changed more during recovery when compared with unaffected networks). This change in connectivity was significantly correlated with clinical changes assessed with the National Institute of Health Stroke Scale. Our results provide evidence that the functional architecture of large-scale networks is critical to understanding the clinical effect and trajectory of post-stroke recovery.

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.

Evaluation of an AIF correction algorithm for dynamic susceptibility contrast-enhanced perfusion MRI.

For longitudinal studies in patients suffering from cerebrovascular diseases the poor reproducibility of perfusion measurements via dynamic susceptibility-weighted contrast-enhanced MRI (DSC-MRI) is a relevant concern. We evaluate a novel algorithm capable of overcoming limitations in DSC-MRI caused by partial volume and saturation issues in the arterial input function (AIF) by a blood flow stimulation-study. In 21 subjects, perfusion parameters before and after administration of blood flow stimulating L-arginine were calculated utilizing a block-circulant singular value decomposition (cSVD). A total of two different raters and three different rater conditions were employed to select AIFs: Besides 1) an AIF selection by an experienced rater, a beginner rater applied a steady state-oriented strategy, returning; 2) raw; and 3) corrected AIFs. Highly significant changes in regional cerebral blood flow (rCBF) by 9.0% (P < 0.01) could only be found when the AIF correction was performed. To further test for improved reproducibility, in a subgroup of seven subjects the baseline measurement was repeated 6 weeks after the first examination. In this group as well, using the correction algorithm decreased the SD of the difference between the two baseline measurements by 42%.