Diagnostic Value of Diffusion Tensor Imaging and Positron Emission Tomography in Early Stages of Frontotemporal Dementia.

BACKGROUND: Due to suboptimal sensitivity and specificity of structural and molecular neuroimaging tools, the diagnosis of behavioral variant frontotemporal dementia (bvFTD) remains challenging. OBJECTIVE: Investigation of the sensitivity of diffusion tensor imaging (DTI) and fluorodeoxyglucose positron emission tomography (FDG-PET) to detect cerebral alterations in early stages of bvFTD despite inconspicuous conventional MRI. METHODS: Thirty patients with early stages of bvFTD underwent a detailed neuropsychological examination, cerebral 3T MRI with DTI analysis, and FDG-PET. After 12 months of follow-up, all patients finally fulfilled the diagnosis of bvFTD. Individual FDG-PET data analyses showed that 20 patients exhibited a "typical" pattern for bvFTD with bifrontal and/or temporal hypometabolism (bvFTD/PET+), and that 10 patients showed a "non-typical"/normal pattern (bvFTD/PET-). DTI data were compared with 42 healthy controls in an individual and voxel-based group analysis. To examine the clinical relevance of the findings, associations between pathologically altered voxels of DTI or FDG-PET results and behavioral symptoms were estimated by linear regression analyses. RESULTS: DTI voxel-based group analyses revealed microstructural degeneration in bifrontal and bitemporal areas in bvFTD/PET+ and bvFTD/PET- groups. However, when comparing the sensitivity of individual DTI data analysis with FDG-PET, DTI appeared to be less sensitive. Neuropsychological symptoms were considerably related to neurodegeneration within frontotemporal areas identified by DTI and FDG-PET. CONCLUSION: DTI seems to be an interesting tool for detection of functionally relevant neurodegenerative alterations in early stages of bvFTD, even in bvFTD/PET- patients. However, at a single subject level, it seems to be less sensitive than FDG-PET. Thus, improvement of individual DTI analysis is necessary.

Gray matter correlates of pressure pain thresholds and self-rated pain sensitivity: a voxel-based morphometry study.

Individual differences in sensitivity to pain are large and have clinical and scientific importance. Although heavily influenced by situational factors, they also relate to genetic factors and psychological traits, and are reflected by differences in functional activation in pain-related brain regions. Here, we used voxel-based morphometry to investigate if individual pain sensitivity is related to local gray matter volumes. Pain sensitivity was determined using (1) index finger pressure pain thresholds (PPTs) and (2) pain intensity ratings of imagined painful situations as assessed by the Pain Sensitivity Questionnaire (PSQ) in 501 population-based subjects participating in the BiDirect Study. Pain Sensitivity Questionnaire scores were positively associated with gray matter in 2 symmetrical clusters, with a focus on the parahippocampal gyrus, extending to the hippocampus, fusiform gyrus, BA19, putamen, and insula (P < 0.05 corrected), but the effect was small (R = 0.045-0.039). No negative associations with the PSQ and no associations with the PPT reached significance. Parahippocampal activation during pain and altered parahippocampal gray matter in chronic pain have been reported, which would be consistent with positive associations with PSQ scores. Alternatively, associations of PSQ scores with the parahippocampal and fusiform gray matter could relate to the visual imagination of painful situations required by the PSQ, not to pain sensitivity itself. Regarding PPTs, the present data obtained in a large sample strongly suggest an absence of associations of this parameter with gray matter volume. In conclusion, the present results argue against a strong association between pain sensitivity and local gray matter volumes.

Sample heterogeneity in unipolar depression as assessed by functional connectivity analyses is dominated by general disease effects.

OBJECTIVES: Combinations of resting-state fMRI and machine-learning techniques are increasingly employed to develop diagnostic models for mental disorders. However, little is known about the neurobiological heterogeneity of depression and diagnostic machine learning has mainly been tested in homogeneous samples. Our main objective was to explore the inherent structure of a diverse unipolar depression sample. The secondary objective was to assess, if such information can improve diagnostic classification. MATERIALS AND METHODS: We analyzed data from 360 patients with unipolar depression and 360 non-depressed population controls, who were subdivided into two independent subsets. Cluster analyses (unsupervised learning) of functional connectivity were used to generate hypotheses about potential patient subgroups from the first subset. The relationship of clusters with demographical and clinical measures was assessed. Subsequently, diagnostic classifiers (supervised learning), which incorporated information about these putative depression subgroups, were trained. RESULTS: Exploratory cluster analyses revealed two weakly separable subgroups of depressed patients. These subgroups differed in the average duration of depression and in the proportion of patients with concurrently severe depression and anxiety symptoms. The diagnostic classification models performed at chance level. LIMITATIONS: It remains unresolved, if subgroups represent distinct biological subtypes, variability of continuous clinical variables or in part an overfitting of sparsely structured data. CONCLUSIONS: Functional connectivity in unipolar depression is associated with general disease effects. Cluster analyses provide hypotheses about potential depression subtypes. Diagnostic models did not benefit from this additional information regarding heterogeneity.

Effects of Different Exercise Strategies and Intensities on Memory Performance and Neurogenesis.

It is well established that physical exercise affects both hippocampal neurogenesis and memory functions. Until now, distinctive effects of controlled and voluntary training (VT) on behavior and neurogenesis as well as interactions between exercise intensity, neurogenesis and memory performance are still elusive. The present study tested the impact of moderate controlled and VT on memory formation and hippocampal neurogenesis and evaluated interactions between exercise performance, learning efficiency and proliferation of progenitor cells in the hippocampus. Our data show that both controlled and VT augmented spatial learning and promoted hippocampal neurogenesis. Regression analysis revealed a significant linear increase of the amount of new hippocampal neurons with increased exercise intensity. Regression analysis of exercise performance on retention memory performance revealed a quadratic, inverted u-shaped relationship between exercise performance and retention of spatial memory. No association was found between the amount of newborn neurons and memory performance. Our results demonstrate that controlled training (CT), if performed with an appropriate combination of speed and duration, improves memory performance and neurogenesis. Voluntary exercise elevates neurogenesis dose dependently to high levels. Best cognitive improvement was achieved with moderate exercise performance.

Reduced fractional anisotropy in patients with major depressive disorder and associations with vascular stiffness.

Previous studies revealed several alterations of the cerebral white matter in patients with major depressive disorder. However, it is unknown if these alterations are associated with vascular changes in the brain and other body parts. We compared diffusion tensor imaging derived fractional anisotropy in a well characterized sample of middle-aged patients with major depressive disorder (n = 290) and never-depressed controls (n = 346) by the method of tract-based spatial statistics. Subsequently, the potential role of pulse wave velocity as a mediator of depression- and age-related changes in extracted estimates of fractional anisotropy were analyzed. The results of the tract-based analysis revealed significantly reduced fractional anisotropy in the left posterior thalamic radiation associated with depression. Analyses of extracted data indicated additional reductions of fractional anisotropy bilaterally in the posterior thalamic radiation and in the left sagittal stratum. The analyses of indirect effects did not show any significant mediation of depression-related effects on fractional anisotropy via pulse wave velocity. However, age-related effects on fractional anisotropy were partially mediated by pulse wave velocity. In conclusion, major depressive disorder is associated with detrimental effects on cerebral white matter microstructure properties which are independent of vascular changes, as measured by pulse wave velocity. However, a portion of age-related detrimental effects on white matter is explained by vascular changes. Longitudinal studies are required for investigating changes in white matter and vascular parameters over time and their association with incident depression.

The Association of Lesion Location and Sleep Related Breathing Disorder in Patients with Acute Ischemic Stroke.

BACKGROUND AND AIMS: Sleep related breathing disorders (SRBD) are common in patients with ischemic stroke and are associated with poor outcome. SRBD after stroke were assumed to be a direct consequence of injury of specific central nervous system structures. However, whether specific locations of ischemic infarcts cause SRBD is yet unknown. We therefore investigated the association of ischemic lesion location with SRBD. METHODS: Patients with acute ischemic stroke treated on our stroke unit were included in a prospective observational study. All patients underwent magnetic resonance imaging (MRI) and polygraphy in the acute phase after stroke. SRBD was defined by an apnea-hypopnea index (AHI) ≥10. MRI were evaluated using standardized maps to depict voxel-wise probability distribution of infarction for patients with and without SRBD. Groups were compared using logistic regression analysis. RESULTS: Of 142 patients included, 86 (59%) had a SRBD. Age, body mass index and prevalence of arterial hypertension were significantly higher in patients with SRBD. There was no statistically significant association between any lesion location and SRBD. CONCLUSION: We found no association of lesion location and SRBD in stroke patients, whereas established risk factors for SRBD, known from general population, were significantly associated with SRBD. Given the high prevalence of SRBD in stroke patients, these findings suggest that cerebral ischemia facilitates the occurrence of SRBD in patients with pre-existing risk factors rather than causing it by damaging specific central nervous system structures. Our findings can be used to identify stroke patients who might benefit from polygraphy screening.

Diagnostic classification of unipolar depression based on resting-state functional connectivity MRI: effects of generalization to a diverse sample.

In small, selected samples, an approach combining resting-state functional connectivity MRI and multivariate pattern analysis has been able to successfully classify patients diagnosed with unipolar depression. Purposes of this investigation were to assess the generalizability of this approach to a large clinically more realistic sample and secondarily to assess the replicability of previously reported methodological feasibility in a more homogeneous subgroup with pronounced depressive symptoms. Two independent subsets were drawn from the depression and control cohorts of the BiDirect study, each with 180 patients with and 180 controls without depression. Functional connectivity either among regions covering the gray matter or selected regions with known alterations in depression was assessed by resting-state fMRI. Support vector machines with and without automated feature selection were used to train classifiers differentiating between individual patients and controls in the entire first subset as well as in the subgroup. Model parameters were explored systematically. The second independent subset was used for validation of successful models. Classification accuracies in the large, heterogeneous sample ranged from 45.0 to 56.1% (chance level 50.0%). In the subgroup with higher depression severity, three out of 90 models performed significantly above chance (60.8-61.7% at independent validation). In conclusion, common classification methods previously successful in small homogenous depression samples do not immediately translate to a more realistic population. Future research to develop diagnostic classification approaches in depression should focus on more specific clinical questions and consider heterogeneity, including symptom severity as an important factor.

MR imaging of the brain in large cohort studies: feasibility report of the population- and patient-based BiDirect study.

OBJECTIVES: To describe the implementation and protocol of cerebral magnetic resonance imaging (MRI) in the longitudinal BiDirect study and to report rates of study participation as well as management of incidental findings. METHODS: Data came from the BiDirect study that investigates the relationship between depression and arteriosclerosis and comprises 2258 participants in three cohorts: 999 patients with depression, 347 patients with manifest cardiovascular disease (CVD) and 912 population-based controls. The study program includes MRI of the brain. Reasons for non-participation were systematically collected. Incidental findings were categorized and disclosed according to clinical relevance. RESULTS: At baseline 2176 participants were offered MRI, of whom 1453 (67 %) completed it. Reasons for non-participation differed according to cohort, age and gender with controls showing the highest participation rate of 79 %. Patient cohorts had higher refusal rates and CVD patients a high prevalence of contraindications. In the first follow-up examination 69 % of participating subjects completed MRI. Incidental findings were disclosed to 246 participants (17 %). The majority of incidental findings were extensive white matter hyperintensities requiring further diagnostic work-up. CONCLUSIONS: Knowledge about subjects and sensible definition of incidental findings are crucial for large-scale imaging projects. Our data offer practical and concrete information for the design of future studies. KEY POINTS: • Willingness to participate in MRI is generally high, also in follow-up examinations. • Rates of refusal and prevalence of contraindications differ according to subject characteristics. • Extensive white matter hyperintensities considerably increase the disclosure rates of incidental findings. • MRI workflow requires continuous case-by-case handling by an interdisciplinary team.

Computed tomography-based quantification of lesion water uptake identifies patients within 4.5 hours of stroke onset: A multicenter observational study.

OBJECTIVE: Many patients with stroke cannot receive intravenous thrombolysis because the time of symptom onset is unknown. We tested whether computed tomography (CT)-based quantification of water uptake in the ischemic tissue can identify patients with stroke onset within 4.5 hours, the time window of thrombolysis. METHODS: Perfusion CT was used to identify ischemic brain tissue, and its density was measured in native CT and related to the density of the corresponding area of the contralateral hemisphere to quantify lesion water uptake. The optimal cutoff value of water uptake distinguishing stroke onset within and beyond 4.5 hours was calculated in patients with proximal middle cerebral artery occlusion (derivation cohort) with known time of symptom onset. The so-derived cutoff value was validated in a prospective cohort from other stroke centers. RESULTS: Of 178 patients of the derivation cohort, 147 (82.6%) had CT within 4.5 hours. Percentage water uptake was significantly lower in patients with stroke onset within compared to beyond 4.5 hours. The area under the receiver operating characteristic curve for distinguishing these patient groups according to percentage water uptake was 0.999 (95% confidence interval = 0.996-1.000, p < 0.001) with an optimal cutoff value of 11.5%. Applying this cutoff to the validation cohort of 240 patients, sensitivity was 98.6%, specificity 90.5%, positive predictive value 99.1%, and negative predictive value 86.4%. INTERPRETATION: Quantification of brain water uptake identifies stroke patients with symptom onset within 4.5 hours with high accuracy and may guide the decision to use thrombolysis in patients with unknown time of stroke onset. Ann Neurol 2016;80:924-934.

Association between major depressive disorder and odor identification impairment.

BACKGROUND: There is evidence of olfactory deficits in patients with major depressive disorder (MDD) but causes and mechanisms are largely unknown. METHODS: We compared 728 patients with current MDD and 555 non-depressed controls regarding odor identification impairment taking into account the severity of acute symptoms and of the disease course. We assessed current symptom severity with the Hamilton Depression Rating Scale, and disease course severity based on admission diagnosis (ICD-10, F32/F33) and self-reported hospitalization frequency, defined as infrequent (<2) and frequent (≥2) depression-related hospitalizations under constant disease duration. A score of <10 on the Sniffin' Sticks-Screen-12 test determined the presence of odor identification impairment. RESULTS: Compared to non-depressed controls patients with frequent (rapidly recurring) hospitalizations had an elevated chance of odor identification impairment, even after adjustment for smell-influencing factors, such as age and smoking, (OR=1.7; 95% CI 1.0-2.9). Patients with recurrent MDD (F33) also had an elevated odds of odor identification impairment compared to those with a first-time episode (F32, OR=1.5; 95% CI 1.0-2.4). In patients with a first-time episode the chance of odor identification impairment increased by 7% with each point increase in the Hamilton Score. LIMITATIONS: Cross-sectional study. Variation in the use of psychotropic medication is a potential bias. CONCLUSION: Odor identification impairment was evident in MDD patients with first-time high symptom severity and in patients with a severe disease course. Whether odor identification impairment is a marker or mediator of structural and functional brain changes associated with acute or active MDD requires further investigations in longitudinal studies.

Outcome After Thrombectomy and Intravenous Thrombolysis in Patients With Acute Ischemic Stroke: A Prospective Observational Study.

BACKGROUND AND PURPOSE: In patients with ischemic stroke, randomized trials showed a better functional outcome after endovascular therapy with new-generation thrombectomy devices compared with medical treatment, including intravenous thrombolysis. However, effects on mortality and the generalizability of results to routine clinical practice are uncertain. METHODS: In a prospective observational register-based study patients with ischemic stroke treated either with thrombectomy, intravenous thrombolysis, or their combination were included. Primary outcome was the modified Rankin scale score (0 [no symptoms] to 6 [death]) at 3 months. Ordinal logistic regression was used to estimate the common odds ratio as treatment effects (shift analysis). Propensity score matching was applied to compare patients treated either with intravenous thrombolysis alone or with intravenous thrombolysis plus thrombectomy. RESULTS: Among 2650 recruited patients, 1543 received intravenous thrombolysis, 504 underwent thrombectomy, and 603 received intravenous thrombolysis in combination with thrombectomy. Later time-to-treatment was associated with worse outcomes among patients treated with thrombectomy plus thrombolysis. In 241 pairs of propensity score-matched patients with a proximal intracranial occlusion, thrombectomy plus thrombolysis was associated with improved functional outcome (common odds ratio, 1.84; 95% confidence interval, 1.32-2.57), and reduced mortality (15% versus 33%; P<0.0001) compared with intravenous thrombolysis alone. Results were similar in various sensitivity analyses accounting for missing outcome data and different analytic methods. CONCLUSIONS: Results from this large prospective registry show that also in routine clinical care thrombectomy plus thrombolysis compared with thrombolysis alone improved functional outcome and reduced mortality in patients with ischemic stroke. Earlier treatment was associated with better outcomes.

Pain Sensitivity in Patients With Major Depression: Differential Effect of Pain Sensitivity Measures, Somatic Cofactors, and Disease Characteristics.

UNLABELLED: Patients with depression often report pain. Evidence regarding altered pain sensitivity in depressed patients remains, however, inconclusive. In a large cross-sectional study we investigated the association between depression and pain sensitivity with regard to 2 different dimensions of pain sensitivity, as well as the effect of somatic cofactors, symptom severity, and subtype of depression. In 735 patients with a current episode of major depression and 456 never-depressed control participants pain thresholds (pressure pain thresholds, PPTs) were measured at the index finger pad and self-rated suprathreshold pain intensity ratings were obtained using the Pain Sensitivity Questionnaire (PSQ)-minor subscore, an instrument that assesses pain intensity in daily life situations. Additionally, lifestyle factors, medical, and psychiatric conditions were assessed. Unadjusted, patients with depression had lower PPTs and higher PSQ-minor scores indicating increased pain sensitivity. After adjusting for potential mediators, such as poor sleep quality and physical inactivity, patients did not differ from control participants regarding PPTs, but still had significantly higher PSQ-minor ratings. Among patients with depression, severity of anxiety symptoms predicted higher PSQ-minor scores. In conclusion, we found a differential effect of depression on the 2 pain sensitivity dimensions: Decreased experimentally obtained pain thresholds were explained by depression-associated somatic factors whereas increased self-rated suprathreshold pain intensity ratings were associated with increased anxiety symptoms. PERSPECTIVE: Because increased pain intensity perception is hypothesized to be a risk factor for the development of chronic pain, our findings may contribute to understanding the high incidence of chronic pain in depressed patients. They also encourage clinicians to consider the role of anxiety in treatment programs for pain in patients with depression.

Diagnostic criteria for Susac syndrome.

BACKGROUND: Susac syndrome is characterised by the triad of encephalopathy with or without focal neurological signs, branch retinal artery occlusions and hearing loss. Establishment of the diagnosis is often delayed because the triad is complete only in a minority of patients at disease onset. This leads to a critical delay in the initiation of appropriate treatment. Our objective was to establish criteria for diagnosis of either definite or probable Susac syndrome. METHOD: The establishment of diagnostic criteria was based on the following three steps: (1) Definition of a reference group of 32 patients with an unambiguous diagnosis of Susac syndrome as assessed by all interdisciplinary experts of the European Susac Consortium (EuSaC) team (EuSaC cohort); (2) selection of diagnostic criteria, based on common clinical and paraclinical findings in the EuSaC cohort and on a review of the literature; and (3) validation of the proposed criteria in the previously published cohort of all Susac cases reported until 2012. RESULTS: Integrating the clinical presentation and paraclinical findings, we propose formal criteria and recommend a diagnostic workup to facilitate the diagnosis of Susac syndrome. More than 90% of the cases in the literature fulfilled the proposed criteria for probable or definite Susac syndrome. We surmise that more patients could have been diagnosed with the recommended diagnostic workup. CONCLUSIONS: We propose diagnostic criteria for Susac syndrome that may help both experts and physicians not familiar with Susac syndrome to make a correct diagnosis and to prevent delayed treatment initiation.

Major depressive disorder: Findings of reduced homotopic connectivity and investigation of underlying structural mechanisms.

Depression has been associated with various alterations in magnetic resonance imaging (MRI) derived resting-state functional connectivity. Recently, homotopic connectivity, defined as functional connectivity between homotopic regions across hemispheres, has been reported to be reduced in patients with major depressive disorder (MDD). However, little is known about structural factors underlying alterations of homotopic connectivity, which would contribute to the understanding of the altered neurophysiological architecture in patients with MDD. We compared 368 patients with MDD and 461 never-depressed controls regarding voxel-mirrored homotopic connectivity (VMHC) and potential underlying mechanisms such as the structural connectivity of the corpus callosum, measured by DTI-derived fractional anisotropy (FA), and left-right symmetries in homotopic gray matter volumes. Compared to controls, patients with MDD exhibited reduced VMHC in the cuneus, putamen, superior temporal gyrus, insula, and precuneus. Within these regions, no differences in left-right symmetries in homotopic gray matter volumes were evident across cohorts. FA of the corpus callosum correlated with VMHC in the entire sample. However, patients with MDD and controls did not differ with regard to callosal FA. The findings indicate that MDD is associated with a loss of interhemispheric synchrony in regions known to be implicated in self-referential and reward processing. They also suggest that additional mechanisms are implicated in altered homotopic connectivity of patients with MDD, other than direct callosal fiber pathways or asymmetries in homotopic gray matter volumes.

Explaining the Decrease of In-Hospital Mortality from Ischemic Stroke.

BACKGROUND: Mortality from ischemic stroke has declined over time. However, little is known about the reasons for the decreased mortality. We therefore aimed to evaluate trends in in-hospital mortality and to identify factors associated with these trends. METHODS: This study was based on a prospective database of 26 hospitals of the Stroke Register of Northwestern Germany, which included 73,614 patients admitted between 2000 and 2011. Time trends in observed (crude) and risk-adjusted in-hospital mortality were assessed. Independent factors associated with death after stroke were evaluated using multivariable logistic regression analysis. RESULTS: The observed in-hospital mortality decreased from 6.6% in 2000 to 4.6% in 2008 (P < 0.001 for trend) and then remained fairly stable. The risk-adjusted mortality decreased from 2.85% in 2000 to 1.86% in 2008 (P < 0.01 for trend) and then increased to 2.32% in 2011. Use of in-hospital treatments including antiplatelets within 48 hours, antihypertensive therapy, statins, antidiabetics, physiotherapy and anticoagulants increased over time and was significantly associated with a decrease in mortality. The association of the year of admission with mortality became insignificant after adjustment for antiplatelet therapy within 48 hours (from OR 0.96; 95% CI, 0.94-0.98, to OR 0.99; 95% CI, 0.97-1.01) and physiotherapy (from OR 0.96; 95% CI, 0.94-0.97, to OR 0.99; 95% CI, 0.97-1.00). CONCLUSIONS: In-hospital mortality decreased by approximately one third between 2000 and 2008. This decline was paralleled by improvements in different in-hospital managements, and we demonstrated that it was partly mediated by early antiplatelet therapy and physiotherapy use.

Associations between depression subtypes, depression severity and diet quality: cross-sectional findings from the BiDirect Study.

BACKGROUND: Depression is supposed to be associated with an unhealthy lifestyle including poor diet. The objective of this study was to investigate differences in diet quality between patients with a clinical diagnosis of depression and population-based controls. Additionally, we aimed to examine effects of specific depression characteristics on diet by analyzing if diet quality varies between patients with distinct depression subtypes, and if depression severity is associated with diet quality. METHODS: The study included 1660 participants from the BiDirect Study (n = 840 patients with depression, n = 820 population-based controls). The psychiatric assessment was based on clinical interviews and a combination of depression scales in order to provide the classification of depression subtypes and severity. Diet quality scores, reflecting the adherence to a healthy dietary pattern, were calculated on the basis of an 18-item food frequency questionnaire. Using analysis of covariance, we calculated adjusted means of diet quality scores and tested differences between groups (adjusted for socio-demographic, lifestyle-, and health-related factors). RESULTS: We found no differences in diet quality between controls and patients with depression if depression was considered as one entity. However, we did find differences between patients with distinct subtypes of depression. Patients with melancholic depression reported the highest diet quality scores, whereas patients with atypical depression reported the lowest scores. Depression severity was not associated with diet quality. CONCLUSIONS: Previous literature has commonly treated depression as a homogeneous entity. However, subtypes of depression may be associated with diet quality in different ways. Further studies are needed to enlighten the diet-depression relationship and the role of distinct depression subtypes.

Volume transition analysis: a new approach to resolve reclassification of brain tissue in repeated MRI scans.

BACKGROUND: Variability in brain tissue volumes derived from magnetic resonance images is attributable to various sources. In quantitative comparisons it is therefore crucial to distinguish between biologically and methodically conditioned variance and to take spatial accordance into account. NEW METHOD: We introduce volume transition analysis as a method that not only provides details on numerical and spatial accordance of tissue volumes in repeated scans but also on voxel shifts between tissue types. Based on brain tissue probability maps, mono- and bidirectional voxel shifts can be examined by explicitly separating volume transitions into source and target. We apply the approach to a set of subject data from repeated intra-scanner (one week and 30 month interval) as well as inter-scanner measurements. RESULTS: In all measurement scenarios, we found similar inter-class transitions of 9.9-15.9% of intracranial volume. The percentage of monodirectional net volume transition however increases from 0.3% in short term intra-scanner to 1.6% in long term intra-scanner and 9.3% in inter-scanner comparisons. COMPARISON WITH EXISTING METHODS: Unlike most routinely used variability measures volume transition analysis is able to monitor reclassifications and thus to quantify not only balanced flows but also the amount of monodirectional net flows between tissue classes. The approach is independent from group analysis and can thus be applied in as few as two images. CONCLUSIONS: The proposed method is an easily applicable tool that is useful in discovering intra-individual brain changes and assists in separating biological from technical variance in structural brain measures.

Feasibility platform for stroke studies: an online tool to improve eligibility criteria for clinical trials.

BACKGROUND AND PURPOSE: Eligibility criteria are a key factor for the feasibility and validity of clinical trials. We aimed to develop an online tool to assess the potential effect of inclusion and exclusion criteria on the proportion of patients eligible for an acute stroke trial. METHODS: We identified relevant inclusion and exclusion criteria of acute stroke trials. Based on these criteria and using a cohort of 1537 consecutive patients with acute ischemic stroke from 3 stroke centers, we developed a web portal feasibility platform for stroke studies (FePASS) to estimate proportions of eligible patients for acute stroke trials. We applied the FePASS resource to calculate the proportion of patients eligible for 4 recent stroke studies. RESULTS: Sixty-one eligibility criteria were derived from 30 trials on acute ischemic stroke. FePASS, publicly available at http://fepass.uni-muenster.de, displays the proportion of patients in percent to assess the effect of varying values of relevant eligibility criteria, for example, age, symptom onset time, National Institutes of Health Stroke Scale, and prestroke modified Rankin Scale, on this proportion. The proportion of eligible patients for 4 recent stroke studies ranged from 2.1% to 11.3%. Slight variations of the inclusion criteria could substantially increase the proportion of eligible patients. CONCLUSIONS: FePASS is an open access online resource to assess the effect of inclusion and exclusion criteria on the proportion of eligible patients for a stroke trial. FePASS can help to design stroke studies, optimize eligibility criteria, and to estimate the potential recruitment rate.

Establishing the bidirectional relationship between depression and subclinical arteriosclerosis--rationale, design, and characteristics of the BiDirect Study.

BACKGROUND: Depression and cardiovascular diseases due to arteriosclerosis are both frequent and impairing conditions. Depression and (subclinical) arteriosclerosis appear to be related in a bidirectional way, and it is plausible to assume a partly joint causal relationship. However, the biological mechanisms and the behavioral pathways that lead from depression to arteriosclerosis and vice versa remain to be exactly determined. METHODS/DESIGN: This study protocol describes the rationale and design of the prospective BiDirect Study that aims at investigating the mutual relationship between depression and (subclinical) arteriosclerosis. BiDirect is scheduled to follow-up three distinct cohorts of individuals ((i) patients with acute depression (N = 999), (ii) patients after an acute cardiac event (N = 347), and (iii) reference subjects from the general population (N = 912)). Over the course of 12 years, four personal examinations are planned to be conducted. The core examination program, which will remain identical across follow-ups, comprises a personal interview (e.g. medical diagnoses, health care utilization, lifestyle and risk behavior), a battery of self-administered questionnaires (e.g. depressive symptoms, readiness to change health behavior, perceived health-related quality of life), sensory (e.g. olfaction, pain) and neuropsychological (e.g. memory, executive functions, emotional processing, manual dexterity) assessments, anthropometry, body impedance measurement, a clinical work-up regarding the vascular status (e.g. electrocardiogram, blood pressure, intima media thickness), the taking of blood samples (serum and plasma, DNA), and structural and functional resonance imaging of the brain (e.g. diffusion tensor imaging, resting-state, emotional faces processing). The present report includes BiDirect-Baseline, the first data collection wave. DISCUSSION: Due to its prospective character, the integration of three distinct cohorts, the long follow-up time window, the diligent diagnosis of depression taking depression subtypes into account, the consideration of relevant comorbidities and risk factors, the assessment of indicators of (subclinical) arteriosclerosis in different vascular territories, and the structural and functional brain imaging that is performed for a large number of participants, the BiDirect Study represents an innovative approach that combines population-based cohorts with sophisticated clinical work-up methods and that holds the potential to overcome many of the drawbacks characterizing earlier investigations.