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 2019;86:452-457.

Subtracted Dynamic MR Perfusion Source Images (sMRP-SI) provide Collateral Blood Flow Assessment in MCA Occlusions and Predict Tissue Fate.

OBJECTIVES: Collateral blood flow is accepted as a predictive factor of tissue fate in ischemic stroke. Thus, we aimed to evaluate a new method derived from MR perfusion source images to assess collateral flow in patients with ICA/MCA occlusions. METHODS: A total of 132 patients of the prospective 1000+ study were examined. MR perfusion source images were assessed according to Δimg_n = img_n + 1 - img_n - 1 using the five-grade Higashida collateral flow rating system. Higashida scores were correlated to mismatch (MM) volume, mismatch ratio, day 6 FLAIR lesion volumes and day 90 mRS. RESULTS: Patients with Higashida scores 3 and 4 had significantly lower admission NIHSS, smaller FLAIR day 6 lesion volumes (p < 0.001) and higher rates of better long-term outcome (mRS 0-2, p = 0.002). There was a linear trend for the association of Higashida grade 1 (p = 0.002) and 2 (p = 0.001) with unfavourable outcome (day 90 mRS 3-6), but no significant association was found for MM volume, MM ratio and day 90 mRS. Inter-rater agreement was 0.58 (95% CI 0.43-0.73) on day 1, 0.70 (95% CI 0.58-0.81) on day 2. CONCLUSION: sMRP-SI Higashida score offers a non-invasive collateral vessel and tissue perfusion assessment of ischemic tissue. The predictive value of Higashida rating proved superior to MM with regard to day 90 mRS. KEY POINTS: • Assessment of collateral flow using subtracted dynamic MR perfusion source imaging (sMRP-SI). • sMRP-SI offers additional information about morphological characteristics of ischemic brain tissue. • sMRP-SI collateral flow assessment proves superior to mismatch volume. • Better collateral flow was significantly associated with better outcome (day 90 mRS).

Comparison of the 2 Most Popular Deconvolution Techniques for the Detection of Penumbral Flow in Acute Stroke.

BACKGROUND AND PURPOSE: Dynamic susceptibility-weighted contrast-enhanced (DSC) magnetic resonance imaging (MRI) is used to identify the tissue-at-risk in acute stroke, but the choice of optimal DSC postprocessing in the clinical setting remains a matter of debate. Using 15O-water positron emission tomography (PET), we validated the performance of 2 common deconvolution methods for DSC-MRI. METHODS: In (sub)acute stroke patients with consecutive MRI and PET imaging, DSC maps were calculated applying 2 deconvolution methods, standard and block-circulant single value decomposition. We used 2 standardized analysis methods, a region of interest-based and a voxel-based analysis, where PET cerebral blood flow masks of <20 mL/100 g per minute (penumbral flow) and gray matter masks were overlaid on DSC parameter maps. For both methods, receiver operating characteristic curve analysis was performed to identify the accuracy of each DSC-MR map for the detection of PET penumbral flow. RESULTS: In 18 data sets (median time after stroke onset: 18 hours; median time PET to MRI: 101 minutes), block-circulant single value decomposition showed significantly better performance to detect PET penumbral flow only for mean transit time maps. Time-to-maximum (Tmax) had the highest performance independent of the deconvolution method. CONCLUSIONS: Block-circulant single value decomposition seems only significantly beneficial for mean transit time maps in (sub)acute stroke. Tmax is likely the most stable deconvolved parameter for the detection of tissue-at-risk using DSC-MRI.

Number of cerebral microbleeds and risk of intracerebral hemorrhage after intravenous thrombolysis.

BACKGROUND AND PURPOSE: Cerebral microbleeds (CMBs) are found in a substantial proportion of patients with ischemic stroke eligible for treatment with intravenous thrombolysis. Until now, there is limited data on the impact of multiple CMBs on occurrence of intracerebral hemorrhage (ICH) after intravenous thrombolysis. METHODS: Between 2008 and 2013, all patients receiving MRI-based intravenous thrombolysis were identified within our prospective thrombolysis register. Number of CMBs was rated on pretreatment T2*-weighted MRI by a rater blinded to clinical data and follow-up. Outcomes of interest were occurrence of symptomatic ICH (sICH) and parenchymal hemorrhage (PH). RESULTS: Among 326 included patients, 52 patients had a single CMB (16.0%), 19 had 2 to 4 CMBs (5.8%), and 10 had ≥5 CMBs (3.1%). Frequency of sICH/PH was 1.2%/5.7% in patients without CMBs, 3.8%/3.8% in patients with a single CMB, 10.5%/21.1% in patients with 2 to 4 CMBs, and 30.0%/30.0% in patients with ≥5 CMBs, respectively (each P for trend<0.01). The unadjusted odds ratio per additional CMB for sICH was 1.19 (95% confidence interval, 1.07-1.33; P<0.01) and for PH was 1.13 (95% confidence interval, 1.03-1.24; P=0.01). Compared with patients without CMBs, both patients with 2 to 4 CMBs (P=0.02/P=0.02) and patients with ≥5 CMBs (P<0.01/P<0.01) had significantly increased odds ratios for sICH and PH, whereas in patients with a single CMB, odds ratios were not significantly increased (P=0.21/P=0.59). The association of CMB burden with sICH/PH remained significant after adjustment for possible confounders (age, age-related white matter changes score, atrial fibrillation, onset-to-treatment time, prior statin use, and systolic blood pressure on admission). CONCLUSIONS: Our findings indicate a higher risk of sICH and PH after intravenous thrombolysis when multiple CMBs are present, with a graded relationship to increasing baseline CMB number.

Development of a Trusted Third Party at a Large University Hospital: Design and Implementation Study.

Background: Pseudonymization has become a best practice to securely manage the identities of patients and study participants in medical research projects and data sharing initiatives. This method offers the advantage of not requiring the direct identification of data to support various research processes while still allowing for advanced processing activities, such as data linkage. Often, pseudonymization and related functionalities are bundled in specific technical and organization units known as trusted third parties (TTPs). However, pseudonymization can significantly increase the complexity of data management and research workflows, necessitating adequate tool support. Common tasks of TTPs include supporting the secure registration and pseudonymization of patient and sample identities as well as managing consent. Objective: Despite the challenges involved, little has been published about successful architectures and functional tools for implementing TTPs in large university hospitals. The aim of this paper is to fill this research gap by describing the software architecture and tool set developed and deployed as part of a TTP established at Charité - Universitätsmedizin Berlin. Methods: The infrastructure for the TTP was designed to provide a modular structure while keeping maintenance requirements low. Basic functionalities were realized with the free MOSAIC tools. However, supporting common study processes requires implementing workflows that span different basic services, such as patient registration, followed by pseudonym generation and concluded by consent collection. To achieve this, an integration layer was developed to provide a unified Representational state transfer (REST) application programming interface (API) as a basis for more complex workflows. Based on this API, a unified graphical user interface was also implemented, providing an integrated view of information objects and workflows supported by the TTP. The API was implemented using Java and Spring Boot, while the graphical user interface was implemented in PHP and Laravel. Both services use a shared Keycloak instance as a unified management system for roles and rights. Results: By the end of 2022, the TTP has already supported more than 10 research projects since its launch in December 2019. Within these projects, more than 3000 identities were stored, more than 30,000 pseudonyms were generated, and more than 1500 consent forms were submitted. In total, more than 150 people regularly work with the software platform. By implementing the integration layer and the unified user interface, together with comprehensive roles and rights management, the effort for operating the TTP could be significantly reduced, as personnel of the supported research projects can use many functionalities independently. Conclusions: With the architecture and components described, we created a user-friendly and compliant environment for supporting research projects. We believe that the insights into the design and implementation of our TTP can help other institutions to efficiently and effectively set up corresponding structures.

Complete early reversal of diffusion-weighted imaging hyperintensities after ischemic stroke is mainly limited to small embolic lesions.

BACKGROUND AND PURPOSE: Case reports have demonstrated complete early reversal of hyperintensities on diffusion-weighted imaging (DWI) after clinically diagnosed stroke. We aimed to investigate systematically the rate and characteristics of reversible diffusion hyperintensities (RDHs) in the first week after stroke. METHODS: Patients with clinical diagnosis of an acute cerebrovascular event and evidence of ischemia on DWI were included. MRI scans were performed on admission, on the following day, and 4 to 7 days after onset of symptoms with DWI and fluid-attenuated inversion recovery. Baseline and follow-up DWIs were coregistered and examined for individual RDHs. Characteristics of patients and of hyperintensities associated with early reversal were identified. RESULTS: We included 153 patients with a median National Institutes of Health Stroke Scale score of 4 (interquartile range, 2-8). In 3 patients (2%), MR images normalized completely. Thirty-seven patients (24%) displayed individual RDHs. Of 611 initial DWI hyperintensities, 97 (16%) reversed. Thirteen percent of the RDHs had corresponding abnormalities on fluid-attenuated inversion recovery images at the third measurement. Median size of the RDHs was 0.029 mL (interquartile range, 0.013-0.055). RDHs were associated with a multiple infarct pattern (odds ratio, 22.1; 95% confidence interval, 4.5-109.7) and symptomatic carotid stenosis (odds ratio, 5.5; 95% confidence interval, 1.4-21.5). Fifty-nine percent of the patients with RDHs had new additional lesions on follow-up DWI. RDHs were not associated with functional improvement on the National Institutes of Health Stroke Scale score. CONCLUSIONS: In this population of mainly minor to moderate stroke patients, complete normalization of MR images was rare. Complete reversal of individual DWI hyperintensities was limited to very small lesions and mostly occurred in embolic stroke patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00715533.

Early new diffusion-weighted imaging lesions appear more often in stroke patients with a multiple territory lesion pattern.

BACKGROUND AND PURPOSE: New diffusion-weighted imaging (DWI) lesions are common in patients with acute ischemic stroke. They are associated with an initial nonsingle lesion pattern. Previous studies have not analyzed this association in detail. We differentiated nonsingle lesions in 1 vascular supply territory only (scattered lesion pattern) from nonsingle lesions in ≥2 vascular supply territory (multiple territory lesion -pattern). METHODS: Patients with an acute ischemic stroke underwent 3 MRI (3T) examinations: on admission, on the following day, and 4 to 7 days after symptom onset. First, DWI lesions were delineated manually by raters blinded to clinical details. Second, DWI images were coregistered and analyzed visually for new hyperintensities. The initial lesion pattern was categorized as single, scattered, or multiple territory. RESULTS: Of 340 patients enrolled, 43% had a single lesion pattern, 40% had a scattered lesion pattern, and 17% had a multiple territory lesion pattern. In multivariable analysis, the categorical variable lesion pattern was independently associated with new DWI lesions (odds ratio multiple territory lesion pattern, 3.64 [95% confidence interval, 1.75-7.58]; odds ratio scattered lesion pattern, 1.96 [95% confidence interval, 1.09-3.56]). Patients with multiple territory lesion pattern had significantly more often diabetes mellitus, and their new lesions were more often located remotely from the initial area of hypoperfusion compared with patients with scattered lesion pattern. CONCLUSION: Lesion pattern on initial image is an independent risk factor for new DWI lesions. The risk for new DWI lesions is highest in patients with multiple territory lesion pattern.

Smoking-thrombolysis paradox: recanalization and reperfusion rates after intravenous tissue plasminogen activator in smokers with ischemic stroke.

BACKGROUND AND PURPOSE: The so-called smoking-thrombolysis paradox of an improved outcome after thrombolysis was first described in smokers with myocardial infarction. We investigated whether reperfusion rates and clinical outcome differ between smokers and nonsmokers with ischemic stroke after intravenous tissue plasminogen activator. METHODS: Consecutive acute ischemic stroke patients, who had magnetic resonance imaging before and 1 day after thrombolysis, were included for analysis. All of the patients received intravenous tissue plasminogen activator within 4.5 hours. Reperfusion was defined as a 75% reduction in perfusion deficit (mean transit time >6 s) after thrombolysis compared with baseline. Magnetic resonance angiography was used to evaluate arterial stenosis and occlusion. Functional outcome was assessed 3 months after stroke using the modified Rankin Score. RESULTS: Of 148 patients, 21.6% were smokers (n=32). Smokers were younger (median, 61 years [SD, 9.4 years] versus 75 years [SD, 11.6 years]; P<0.001), less often women (28% versus 51%; P=0.03), had lower baseline glucose levels (median, 6.2 mmol/L [interquartile range, 5.7-6.8 mmol/L] versus 6.7 mmol/L [interquartile range, 6.1-8.2 mmol/L]; P<0.01) and higher baseline perfusion deficits (median, 53 mL [interquartile range, 13-141 mL] versus 17 mL [interquartile range, 2-66 mL]; P=0.04). In a backward stepwise regression analysis including age, sex, hypertension, glucose, perfusion deficit, and smoking, smoking had an odds ratio of 4 (95% confidence interval, 1-16; P=0.03) for reperfusion and 6 (95% confidence interval, 1-30; P=0.05) for recanalization (regression analysis for recanalization also included localization of arterial occlusion). Smokers had a better outcome (modified Rankin Score=0-2) than nonsmokers (77% versus 55%; P=0.05). CONCLUSIONS: Smoking is independently associated with recanalization and reperfusion, indicating that thrombolytic therapy acts more effectively in smokers; because of small numbers, these results should be considered preliminary. Clinical Trial Registration- URL: http://clinicaltrials.gov. Unique Identifier: NCT00715533.

Biomarkers and perfusion--training-induced changes after stroke (BAPTISe): protocol of an observational study accompanying a randomized controlled trial.

BACKGROUND: Physical activity is believed to exert a beneficial effect on functional and cognitive rehabilitation of patients with stroke. Although studies have addressed the impact of physical exercise in cerebrovascular prevention and rehabilitation, the underlying mechanisms leading to improvement are poorly understood. Training-induced increase of cerebral perfusion is a possible mediating mechanism. Our exploratory study aims to investigate training-induced changes in blood biomarker levels and magnetic resonance imaging in patients with subacute ischemic stroke. METHODS/DESIGN: This biomarker-driven study uses an observational design to examine a subgroup of patients in the randomized, controlled PHYS-STROKE trial. In PHYS-STROKE, 215 patients with subacute stroke (hemorrhagic and ischemic) receive either 4 weeks of physical training (aerobic training, 5 times a week, for 50 minutes) or 4 weeks of relaxation sessions (5 times a week, for 50 minutes). A convenience sample of 100 of these patients with ischemic stroke will be included in BAPTISe and will receive magnetic resonance imaging (MRI) scans and an additional blood draw before and after the PHYS-STROKE intervention. Imaging scans will address parameters of cerebral perfusion, vessel size imaging, and microvessel density (the Q factor) to estimate the degree of neovascularization in the brain. Blood tests will determine several parameters of immunity, inflammation, endothelial function, and lipometabolism. Primary objective of this study is to evaluate differential changes in MRI and blood-derived biomarkers between groups. Other endpoints are next cerebrovascular events and functional status of the patient after the intervention and after 3 months assessed by functional scores, in particular walking speed and Barthel index (co-primary endpoints of PHYS-STROKE). Additionally, we will assess the association between functional outcomes and biomarkers including imaging results. For all endpoints we will compare changes between patients who received physical fitness training and patients who had relaxation sessions. DISCUSSION: This exploratory study will be the first to investigate the effects of physical fitness training in patients with ischemic stroke on MRI-based cerebral perfusion, pertinent blood biomarker levels, and functional outcome. The study may have an impact on current patient rehabilitation strategies and reveal important information about the roles of MRI and blood-derived biomarkers in ischemic stroke. TRIAL REGISTRATION: NCT01954797.

Incidence of new diffusion-weighted imaging lesions outside the area of initial hypoperfusion within 1 week after acute ischemic stroke.

BACKGROUND AND PURPOSE: New diffusion-weighted imaging (DWI) lesions are common in patients with acute ischemic stroke. The pathophysiology of these new lesions is unclear. We differentiated new DWI lesions outside the area of initial hypoperfusion from those confined to the area of initial hypoperfusion. METHODS: Patients with acute stroke underwent 3 MRI examinations: on admission, on the next day, and 4 to 7 days after symptom onset. Patients were included if a perfusion deficit was present on the initial scan. Lesions on DWI images were delineated manually. Coregistered DWI images were analyzed visually for new hyperintensities. In reference to the perfusion maps (mean transit time), patients were classified as having "outside lesions" if new DWI lesions were outside or both outside and inside the area of the initial perfusion deficit or "inside lesions" if new DWI lesions were completely inside. RESULTS: We enrolled 164 patients. Thirty-eight patients (23%) had outside lesions and 34 patients (21%) had inside lesions. In multivariable regression analysis, new outside lesions were significantly associated with symptomatic carotid stenosis, multiple index lesions pattern, and high low-density lipoprotein levels. New inside lesions were significantly associated with (spontaneous or thrombolytic) vessel recanalization, multiple index lesions pattern, and low low-density lipoprotein levels. CONCLUSIONS: Outside and inside lesions represent different pathophysiological entities. More specifically patients with outside lesions may have an increased risk for subsequent cerebrovascular events.

Fluid-attenuated inversion recovery images and stroke outcome after thrombolysis.

BACKGROUND AND PURPOSE: We investigated if hyperintensities on fluid-attenuated inversion recovery (FLAIR) sequences in arteries and parenchyma are associated with poor outcome 3 months after thrombolysis. METHODS: Consecutive acute stroke patients with known time of symptom onset who had an MRI before and 1 day after thrombolysis were included in this study. Blinded to follow-up imaging and outcome, 2 raters independently judged the presence or absence of arterial and parenchymal FLAIR hyperintensities. Functional outcome (modified Rankin Scale) was assessed after 3 months. RESULTS: Out of 90 patients, 22 had parenchymal FLAIR hyperintensities and 42 had hyperintense vessels. The combination of FLAIR hyperintensities in arteries and parenchyma occurred in 15 patients. Stepwise forward regression analysis revealed an adjusted odds ratio of 14.5 for a worse outcome (modified Rankin Scale score >2) in patients with FLAIR hyperintensities in arteries and parenchyma (95% confidence interval, 1.3-158.5; P=0.03). CONCLUSIONS: FLAIR hyperintensities in arteries and parenchyma are an easy-to-use MRI feature in acute ischemic stroke associated with poor outcome 3 months after thrombolysis.

Thalamic sensory strokes with and without pain: differences in lesion patterns in the ventral posterior thalamus.

OBJECTIVE: Vascular lesions of the posterolateral thalamus typically result in a somatosensory syndrome in which some patients develop central neuropathic post-stroke pain (CPSP). Damage to the spinothalamic tract terminus is assumed to be a prerequisite for thalamic CPSP. At the nuclear level, it remains a matter of debate whether the ventral posterolateral nucleus (VPL) or the posterior portion of the ventral medial nucleus (VMpo) constitutes the decisive lesion site. The hypothesis of the study was that lesion location in thalamic CPSP patients differs from that in thalamic stroke patients without pain, and the aim was to identify whether this difference comprises the VPL and/or the VMpo. DESIGN: 30 patients with chronic thalamic stroke and a persistent contralateral somatosensory syndrome were examined. CPSP patients (n=18) were compared with non-pain control patients. By coregistration of a digitised thalamic atlas with T1 weighted MR images, lesion clusters were allocated to the thalamic nuclei. RESULTS: VPL was affected in both groups, but CPSP lesion clusters comprised the more posterior, inferior and lateral parts of the VPL compared with controls. Additional partial involvement of the VMpo was seen in only three pain patients. In three other pain patients, lesions involved neither the VPL nor the VMpo, but mainly affected the anterior pulvinar. CONCLUSION: This study specifies the role of the VPL in thalamic CPSP and shows that the posterolateratal and inferior parts in particular are critically lesioned in pain patients. In this thalamic subregion, afferents of the spinothalamic tract are known to terminate. In contrast, the data do not support a pivotal impact of the VMpo on thalamic CPSP.

Silent new DWI lesions within the first week after stroke.

BACKGROUND: The rate of cerebral infarct recurrence is determined by clinical examination. Routine neurological examination is less sensitive than cerebral imaging in detecting new cerebral lesions. We aimed to determine the rate of new diffusion-weighted imaging (DWI) lesions at 2 time points after stroke and to identify factors associated with them. METHODS: Patients who were hospitalized with acute ischemic stroke underwent DWI at 3 time points (within 24, 48 and 144 h after stroke onset, respectively). Scans were made anonymous and reviewed in a random order. Lesions on DWI were delineated manually by blinded investigators. Then, coregistered DWI templates were analyzed for new ischemic lesions on the corresponding follow-up DWI. New lesions had to be separate and lesion growth was not considered. Univariate and multivariable logistic regression analyses were performed to define predictors of new DWI lesions. RESULTS: A total of 159 patients were enrolled in the study. Clinical stroke recurrence was detected in 2.5% of patients. A new cerebral lesion was detected in 5.7% of patients between first and second imaging (first interval) and 23.3% between second and third imaging (second interval). In univariate analyses, thrombolysis and multiple lesion pattern were associated with new lesions within the first interval. Ipsilateral carotid stenosis, multiple lesion pattern, vessel recanalization, atrial fibrillation, older age and higher NIHSS were associated with new lesions within the second interval. In multivariable analysis, ipsilateral carotid stenosis, recanalization and multiple lesion pattern remained independently associated with any new lesions. CONCLUSIONS: New DWI lesions occur more often than routine neurological examination suggests. Thrombolysis was associated with very early new DWI lesions within the first interval, ipsilateral carotid stenosis and spontaneous recanalization with new DWI lesions within the second interval.

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

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.

Critical assessment of transformer-based AI models for German clinical notes.

Objective: Healthcare data such as clinical notes are primarily recorded in an unstructured manner. If adequately translated into structured data, they can be utilized for health economics and set the groundwork for better individualized patient care. To structure clinical notes, deep-learning methods, particularly transformer-based models like Bidirectional Encoder Representations from Transformers (BERT), have recently received much attention. Currently, biomedical applications are primarily focused on the English language. While general-purpose German-language models such as GermanBERT and GottBERT have been published, adaptations for biomedical data are unavailable. This study evaluated the suitability of existing and novel transformer-based models for the German biomedical and clinical domain. Materials and Methods: We used 8 transformer-based models and pre-trained 3 new models on a newly generated biomedical corpus, and systematically compared them with each other. We annotated a new dataset of clinical notes and used it with 4 other corpora (BRONCO150, CLEF eHealth 2019 Task 1, GGPONC, and JSynCC) to perform named entity recognition (NER) and document classification tasks. Results: General-purpose language models can be used effectively for biomedical and clinical natural language processing (NLP) tasks, still, our newly trained BioGottBERT model outperformed GottBERT on both clinical NER tasks. However, training new biomedical models from scratch proved ineffective. Discussion: The domain-adaptation strategy's potential is currently limited due to a lack of pre-training data. Since general-purpose language models are only marginally inferior to domain-specific models, both options are suitable for developing German-language biomedical applications. Conclusion: General-purpose language models perform remarkably well on biomedical and clinical NLP tasks. If larger corpora become available in the future, domain-adapting these models may improve performances.

Structured, Harmonized, and Interoperable Integration of Clinical Routine Data to Compute Heart Failure Risk Scores.

Risk prediction in patients with heart failure (HF) is essential to improve the tailoring of preventive, diagnostic, and therapeutic strategies for the individual patient, and effectively use health care resources. Risk scores derived from controlled clinical studies can be used to calculate the risk of mortality and HF hospitalizations. However, these scores are poorly implemented into routine care, predominantly because their calculation requires considerable efforts in practice and necessary data often are not available in an interoperable format. In this work, we demonstrate the feasibility of a multi-site solution to derive and calculate two exemplary HF scores from clinical routine data (MAGGIC score with six continuous and eight categorical variables; Barcelona Bio-HF score with five continuous and six categorical variables). Within HiGHmed, a German Medical Informatics Initiative consortium, we implemented an interoperable solution, collecting a harmonized HF-phenotypic core data set (CDS) within the openEHR framework. Our approach minimizes the need for manual data entry by automatically retrieving data from primary systems. We show, across five participating medical centers, that the implemented structures to execute dedicated data queries, followed by harmonized data processing and score calculation, work well in practice. In summary, we demonstrated the feasibility of clinical routine data usage across multiple partner sites to compute HF risk scores. This solution can be extended to a large spectrum of applications in clinical care.

Fully automated postprocessing carries a risk of substantial overestimation of perfusion deficits in acute stroke magnetic resonance imaging.

BACKGROUND AND PURPOSE: Due to the risk of rater bias and time restrictions in clinical practice, an automated approach to delineation of hypoperfused tissue in patients with acute ischemic stroke would be preferred to a manual one. We tested the hypothesis that existing software solutions, on account of numerous artifacts, produce hypoperfused tissue even in a cohort of patients with no ischemia. METHODS: Thirty-nine patients, all admitted for exclusion of cerebral ischemia or hemorrhage and without a final diagnosis of stroke imaged between September 2008 and May 2009 were included in the study. Using 3 different software packages (PerfScape/NeuroScape, PMA and Stroketool), perfusion maps of mean transit time, cerebral blood flow and T(max) were created for each patient. Three different thresholds were applied to each parameter map, and subsequent volumes of hypoperfused tissue were calculated. RESULTS: The median volume of hypoperfused tissue for all the subjects was 92.9 ml (interquartile range, IQR: 13.3-323.4 ml) when calculated by PerfScape/NeuroScape, 30.42 ml (IQR: 13.9-71.4 ml) when calculated by PMA and 78.71 ml (IQR: 40.3-140.8 ml) when calculated by Stroketool. The volumes derived via the different software applications mostly showed only a weak-to-moderate association with each other (Spearman's correlation coefficient between 0.02 and 0.76). CONCLUSIONS: Although automated protocols show promise, the programs Stroketool, PerfScape and PMA require substantial improvement in order to be able to automatically and reliably differentiate between patients with a credible region of ischemia-related hypoperfusion and those without.

Search for a map and threshold in perfusion MRI to accurately predict tissue fate: a protocol for assessing lesion growth in patients with persistent vessel occlusion.

BACKGROUND: The MRI-based mismatch concept has been used to estimate the risk of infarction in ischemic stroke. Based on multiple studies on magnetic resonance perfusion imaging, it seems unlikely that any perfusion parameter threshold will provide a reliable prediction of radiological or clinical outcome for all patients. The goal of our study was to find a minimally biased yet maximally useful perfusion postprocessing protocol which would offer the treating physician a useful estimate of tissue fate. METHODS: One hundred and forty-five acute ischemic stroke patients, admitted within 24 h after stroke to the Charité-University Medicine Hospital in Berlin between March 2008 and November 2009, were included in this study. Using three different software packages (Perfscape/Neuroscape, PMA and Stroketool), maps of mean transit time, cerebral blood flow (CBF) and T(max) were created. Three different thresholds were applied on each parameter map and subsequent volumes of hypoperfused tissue were calculated. RESULTS: Overall, the maps and thresholds giving the least amount of overestimation of the final infarct volume were T(max) 8 s in Perfscape/Neuroscape, CBF 20 ml/100 g/min in PMA and CBF 15% (of the highest value on the scale for a given patient) in Stroketool. In patients with persistent vessel occlusion, a CBF map with a restrictive threshold showed volumes of tissue at definite risk of infarction in up to 100% of patients. The additional use of a CBF map with a high threshold enabled identification of patients without penumbras. CONCLUSIONS: No combination of software, map and threshold was able to give a reliable estimate of tissue fate for either all patients or any subgroup of patients. However, in patients with vessel occlusion, combination of a CBF map with a low and a high threshold can enable calculation of the minimum volume of brain tissue that will inevitably be lost if the occlusion persists.

Fluid-attenuated inversion recovery evolution within 12 hours from stroke onset: a reliable tissue clock?

BACKGROUND AND PURPOSE: It has recently been proposed that fluid-attenuated inversion recovery (FLAIR) imaging may serve as a surrogate marker for time of symptom onset after stroke. We assessed the hypothesis that FLAIR imaging could be used to decide if an MRI was performed within 4.5 hours from symptom onset or later. METHODS: All consecutive patients with presumed stroke who underwent an MRI within 12 hours after known symptom onset were included regardless of stroke subtype and severity between May 2008 and May 2009. Blinded to time of symptom onset, 2 raters judged the visibility of lesions on FLAIR. Apparent diffusion coefficient values, lesion volume on diffusion-weighted imaging, and relative signal intensity of FLAIR lesions were determined. RESULTS: In 94 consecutive patients with stroke, we found that median time from symptom onset for FLAIR-positive patients (189 minutes; interquartile range, 110 to 369 minutes) was significantly longer compared with FLAIR-negative patients (103 minutes; interquartile range, 75 to 183 minutes; P=0.011). Negative FLAIR had a sensitivity of 46% and a specificity of 79% for allocating patients to a time window of less than 4.5 hours. FLAIR positivity increased with diffusion-weighted imaging lesion volume (P<0.001) but showed no correlation with apparent diffusion coefficient values (P=0.795). There was no significant correlation between relative signal intensity and time from symptom onset (Spearman correlation coefficient -0.152, P=0.128). CONCLUSIONS: Based on our findings, we cannot recommend the use of FLAIR visibility as an estimate of time from symptom onset within the first 4.5 hours.

Clinical and radiological courses do not differ between fluid-attenuated inversion recovery-positive and negative patients with stroke after thrombolysis.

BACKGROUND AND PURPOSE: After acute ischemic stroke, the proportion of patients with detectable lesions on fluid-attenuated inversion recovery (FLAIR) MRI sequences increases over time. We investigated whether thrombolysis was less effective in FLAIR-positive versus -negative patients. METHODS: In this single-center hospital-based study, all consecutive patients with ischemic stroke who underwent an MRI before and 24 hours after thrombolysis between May 2008 and October 2009 were included. Patients were included if exact time of onset was known and thrombolysis was performed within 3 hours up until August 2008 and within 4.5 hours from September 2008 on. Blinded to time of symptom onset, 3 raters independently judged the visibility of lesions on FLAIR. Lesion volumes on diffusion-weighted imaging as well as National Institutes of Health Stroke Scale before and 1 day after thrombolysis were determined. RESULTS: Of 51 patients (25 females, mean age 71, median National Institutes of Health Stroke Scale 6), 26 were FLAIR-positive. Neither lesion growth nor change in National Institutes of Health Stroke Scale differed significantly between FLAIR-positive versus -negative patients: median growth 2.6 mL (interquartile growth, -0.1 to 17.6) versus 0.8 mL (interquartile range, 0.1 to 17.8) and change in National Institutes of Health Stroke Scale -2.5 (interquartile range, -5 to 0) versus -2.0 (interquartile range, -5 to 0.5), respectively (P>0.5, Mann-Whitney rank sum test). CONCLUSIONS: Visibility of lesions on FLAIR in areas of diffusion restriction was not predictive of the response to thrombolysis.