Technical considerations of multi-parametric tissue outcome prediction methods in acute ischemic stroke patients.

Decisions regarding acute stroke treatment rely heavily on imaging, but interpretation can be difficult for physicians. Machine learning methods can assist clinicians by providing tissue outcome predictions for different treatment approaches based on acute multi-parametric imaging. To produce such clinically viable machine learning models, factors such as classifier choice, data normalization, and data balancing must be considered. This study gives comprehensive consideration to these factors by comparing the agreement of voxel-based tissue outcome predictions using acute imaging and clinical parameters with manual lesion segmentations derived from follow-up imaging. This study considers random decision forest, generalized linear model, and k-nearest-neighbor machine learning classifiers in conjunction with three data normalization approaches (non-normalized, relative to contralateral hemisphere, and relative to contralateral VOI), and two data balancing strategies (full dataset and stratified subsampling). These classifier settings were evaluated based on 90 MRI datasets from acute ischemic stroke patients. Distinction was made between patients recanalized using intraarterial and intravenous methods, as well as those without successful recanalization. For primary quantitative comparison, the Dice metric was computed for each voxel-based tissue outcome prediction and its corresponding follow-up lesion segmentation. It was found that the random forest classifier outperformed the generalized linear model and the k-nearest-neighbor classifier, that normalization did not improve the Dice score of the lesion outcome predictions, and that the models generated lesion outcome predictions with higher Dice scores when trained with balanced datasets. No significant difference was found between the treatment groups (intraarterial vs intravenous) regarding the Dice score of the tissue outcome predictions.

Neuroradiologic Characteristics of Primary Angiitis of the Central Nervous System According to the Affected Vessel Size.

INTRODUCTION: Magnetic resonance imaging (MRI) has an important impact in diagnosing primary angiitis of the central nervous system (PACNS). However, neuroradiologic findings may vary immensely, making an easy and definite diagnosis challenging. METHODS: In this retrospective, single center study, we analyzed neuroradiologic findings of patients with PACNS diagnosed at our hospital between 2009 and 2014. Furthermore, we classified patients according to the affected vessel size and compared imaging characteristics between the subgroups. RESULTS: Thirty-three patients were included (mean age 43 [±15.3] years, 17 females) in this study. Patients with positive angiographic findings were classified as either medium or large vessel PACNS and presented more ischemic lesions (p < 0.001) and vessel wall enhancement (p = 0.017) compared to patients with small vessel PACNS. No significant differences were detected for the distribution of contrast-enhancing lesions (parenchymal or leptomeningeal), hemorrhages, or lesions with mass effect. Twenty-five patients underwent brain biopsy. Patients with medium or large vessel PACNS were less likely to have positive biopsy results. DISCUSSION: It is essential to differentiate between small and medium/large vessel PACNS since results in MRI, digital subtraction angiography and brain biopsy may differ immensely. Since image quality of MR scanners improves gradually and brain biopsy may often be nonspecific or negative, our results emphasize the importance of MRI/MRA in the diagnosis process of PACNS.

Evaluation and reduction of magnetic resonance imaging artefacts induced by distinct plates for osseous fixation: an in vitro study @ 3 T.

OBJECTIVES:: To analyze MRI artefacts induced at 3 T by bioresorbable, titanium (TI) and glass fibre reinforced composite (GFRC) plates for osseous reconstruction. METHODS:: Fixation plates including bioresorbable polymers (Inion CPS, Inion Oy, Tampere, Finland; Rapidsorb, DePuy Synthes, Umkirch, Germany; Resorb X, Gebrueder KLS Martin GmbH, Tuttlingen, Germany), GFRC (Skulle Implants Oy, Turku, Finland) and TI plates of varying thickness and design (DePuy Synthes, Umkirch, Germany) were embedded in agarose gel and a 3 T MRI was performed using a standard protocol for head and neck imaging including T1W and T2W sequences. Additionally, different artefact reduction techniques (slice encoding for metal artefact reduction & ultrashort echo time) were used and their impact on the extent of artefacts evaluated for each material. RESULTS:: All TI plates induced significantly more artefacts than resorbable plates in T1W and T2W sequences. GFRCs induced the least artefacts in both sequences. The total extent of artefacts increased with plate thickness and height. Plate thickness had no influence on the percentage of overestimation in all three dimensions. TI-induced artefacts were significantly reduced by both artefact reduction techniques. CONCLUSIONS:: Polylactide, GFRC and magnesium plates produce less susceptibility artefacts in MRI compared to TI, while the dimensions of TI plates directly influence artefact extension. Slice encoding for metal artefact reduction and ultrashort echo time significantly reduce metal artefacts at the expense of scan time or image resolution.

Using 3D spatial correlations to improve the noise robustness of multi component analysis of 3D multi echo quantitative T2 relaxometry data.

PURPOSE: We present a computationally feasible and iterative multi-voxel spatially regularized algorithm for myelin water fraction (MWF) reconstruction. This method utilizes 3D spatial correlations present in anatomical/pathological tissues and underlying B1+-inhomogeneity or flip angle inhomogeneity to enhance the noise robustness of the reconstruction while intrinsically accounting for stimulated echo contributions using T2-distribution data alone. METHODS: Simulated data and in vivo data acquired using 3D non-selective multi-echo spin echo (3DNS-MESE) were used to compare the reconstruction quality of the proposed approach against those of the popular algorithm (the method by Prasloski et al.) and our previously proposed 2D multi-slice spatial regularization spatial regularization approach. We also investigated whether the inter-sequence correlations and agreements improved as a result of the proposed approach. MWF-quantifications from two sequences, 3DNS-MESE vs 3DNS-gradient and spin echo (3DNS-GRASE), were compared for both reconstruction approaches to assess correlations and agreements between inter-sequence MWF-value pairs. MWF values from whole-brain data of six volunteers and two multiple sclerosis patients are being reported as well. RESULTS: In comparison with competing approaches such as Prasloski's method or our previously proposed 2D multi-slice spatial regularization method, the proposed method showed better agreements with simulated truths using regression analyses and Bland-Altman analyses. For 3DNS-MESE data, MWF-maps reconstructed using the proposed algorithm provided better depictions of white matter structures in subcortical areas adjoining gray matter which agreed more closely with corresponding contrasts on T2-weighted images than MWF-maps reconstructed with the method by Prasloski et al. We also achieved a higher level of correlations and agreements between inter-sequence (3DNS-MESE vs 3DNS-GRASE) MWF-value pairs. CONCLUSION: The proposed algorithm provides more noise-robust fits to T2-decay data and improves MWF-quantifications in white matter structures especially in the sub-cortical white matter and major white matter tract regions.

Hemodynamic Forces Tune the Arrest, Adhesion, and Extravasation of Circulating Tumor Cells.

Metastatic seeding is driven by cell-intrinsic and environmental cues, yet the contribution of biomechanics is poorly known. We aim to elucidate the impact of blood flow on the arrest and the extravasation of circulating tumor cells (CTCs) in vivo. Using the zebrafish embryo, we show that arrest of CTCs occurs in vessels with favorable flow profiles where flow forces control the adhesion efficacy of CTCs to the endothelium. We biophysically identified the threshold values of flow and adhesion forces allowing successful arrest of CTCs. In addition, flow forces fine-tune tumor cell extravasation by impairing the remodeling properties of the endothelium. Importantly, we also observe endothelial remodeling at arrest sites of CTCs in mouse brain capillaries. Finally, we observed that human supratentorial brain metastases preferably develop in areas with low perfusion. These results demonstrate that hemodynamic profiles at metastatic sites regulate key steps of extravasation preceding metastatic outgrowth.

Rapid fully automatic segmentation of subcortical brain structures by shape-constrained surface adaptation.

This work presents a novel approach for the rapid segmentation of clinically relevant subcortical brain structures in T1-weighted MRI by utilizing a shape-constrained deformable surface model. In contrast to other approaches for segmenting brain structures, its design allows for parallel segmentation of individual brain structures within a flexible and robust hierarchical framework such that accurate adaptation and volume computation can be achieved within a minute of processing time. Furthermore, adaptation is driven by local and not global contrast, potentially relaxing requirements with respect to preprocessing steps such as bias-field correction. Detailed evaluation experiments on more than 1000 subjects, including comparisons to FSL FIRST and FreeSurfer as well as a clinical assessment, demonstrate high accuracy and test-retest consistency of the presented segmentation approach, leading, for example, to an average segmentation error of less than 0.5 mm. The presented approach might be useful in both, research as well as clinical routine, for automated segmentation and volume quantification of subcortical brain structures in order to increase confidence in the diagnosis of neuro-degenerative disorders, such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, or clinical applications for other neurologic and psychiatric diseases.

Patients with primary biliary cholangitis and fatigue present with depressive symptoms and selected cognitive deficits, but with normal attention performance and brain structure.

BACKGROUND: In primary biliary cholangitis (PBC) fatigue is a major clinical challenge of unknown etiology. By demonstrating that fatigue in PBC is associated with an impaired cognitive performance, previous studies have pointed out the possibility of brain abnormalities underlying fatigue in PBC. Whether structural brain changes are present in PBC patients with fatigue, however, is unclear. To evaluate the role of structural brain abnormalities in PBC patients severely affected from fatigue we, therefore, performed a case-control cerebral magnetic resonance imaging (cMRI) study and correlated changes of white and grey brain matter with the cognitive and attention performance. METHODS: 20 female patients with PBC and 20 female age-matched controls were examined in this study. The assessment of fatigue, psychological symptoms, cognitive and attention performance included clinical questionnaires, established cognition tests and a computerized test battery of attention performance. T1-weighted cMRI and diffusion tensor imaging (DTI) scans were acquired with a 3 Tesla scanner. Structural brain alterations were investigated with voxel-based morphometry (VBM) and DTI analyses. Results were correlated to the cognitive and attention performance. RESULTS: Compared to healthy controls, PBC patients had significantly higher levels of fatigue and associated psychological symptoms. Except for an impairment of verbal fluency, no cognitive or attention deficits were found in the PBC cohort. The VBM and DTI analyses revealed neither major structural brain abnormalities in the PBC cohort nor correlations with the cognitive and attention performance. CONCLUSIONS: Despite the high burden of fatigue and selected cognitive deficits, the attention performance of PBC patients appears to be comparable to healthy people. As structural brain alterations do not seem to be present in PBC patients with fatigue, fatigue in PBC must be regarded as purely functional. Future studies should evaluate, whether functional brain changes underlie fatigue in PBC.

Intraparenchymal Hyperattenuations on Flat-Panel CT Directly After Mechanical Thrombectomy are Restricted to the Initial Infarct Core on Diffusion-Weighted Imaging.

PURPOSE: The presence of intraparenchymal hyperattenuations (IPH) on flat-panel computed tomography (FP-CT) after endovascular recanalization in stroke patients is a common phenomenon. They are thought to occur in ischemic areas with breakdown of the blood-brain barrier but previous studies that investigated a mutual interaction are scarce. We aimed to assess the relationship of IPH localization with prethrombectomy diffusion-weighted imaging (DWI) lesions. METHODS: This retrospective multicenter study included 27 acute stroke patients who underwent DWI prior to FP-CT following mechanical thrombectomy. After software-based coregistration of DWI and FP-CT, lesion volumetry was conducted and overlapping was analyzed. RESULTS: Two different patterns were observed: IPH corresponding to the DWI lesion and IPH exceeding the DWI lesion. The latter showed demarcated infarction of DWI exceeding IPH at 24 h. No major hemorrhage following IPH was observed. Most IPH were manifested within the basal ganglia and insular cortex. CONCLUSION: The IPH primarily appeared within the initial ischemic core and secondarily within the penumbral tissue that progressed to infarction. The IPH represent the minimum final infarct volume, which may help in periinterventional decision making.

Can resistance training impact MRI outcomes in relapsing-remitting multiple sclerosis?

BACKGROUND: Multiple sclerosis (MS) is characterised by accelerated brain atrophy, which relates to disease progression. Previous research shows that progressive resistance training (PRT) can counteract brain atrophy in other populations. OBJECTIVE: To evaluate the effects of PRT by magnetic resonance imaging (MRI) and clinical measures of disease progression in people with MS. METHODS: This study was a 24-week randomised controlled cross-over trial, including a Training ( n = 18, 24 weeks of PRT followed by self-guided physical activity) and Waitlist group ( n = 17, 24 weeks of habitual lifestyle followed by PRT). Assessments included disability measures and MRI (lesion load, global brain volume, percentage brain volume change (PBVC) and cortical thickness). RESULTS: While the MS Functional Composite score improved, Expanded Disability Status Scale, lesion load and global brain volumes did not differ between groups. PBVC tended to differ between groups and higher absolute cortical thickness values were observed in 19 of 74 investigated cortical regions after PRT. Observed changes were confirmed and reproduced when comparing relative cortical thickness changes between groups for four areas: anterior cingulate gyrus, temporal pole, orbital sulcus and inferior temporal sulcus. CONCLUSION: PRT seem to induce an increase in cortical thickness, indicating that PRT have a neuroprotective or even neuroregenerative effect in relapsing-remitting MS.

Computed Tomography-Based Imaging of Voxel-Wise Lesion Water Uptake in Ischemic Brain: Relationship Between Density and Direct Volumetry.

OBJECTIVES: Net water uptake per volume of brain tissue may be calculated by computed tomography (CT) density, and this imaging biomarker has recently been investigated as a predictor of lesion age in acute stroke. However, the hypothesis that measurements of CT density may be used to quantify net water uptake per volume of infarct lesion has not been validated by direct volumetric measurements so far. The purpose of this study was to (1) develop a theoretical relationship between CT density reduction and net water uptake per volume of ischemic lesions and (2) confirm this relationship by quantitative in vitro and in vivo CT image analysis using direct volumetric measurements. MATERIALS AND METHODS: We developed a theoretical rationale for a linear relationship between net water uptake per volume of ischemic lesions and CT attenuation. The derived relationship between water uptake and CT density was tested in vitro in a set of increasingly diluted iodine solutions with successive CT measurements. Furthermore, the consistency of this relationship was evaluated using human in vivo CT images in a retrospective multicentric cohort. In 50 edematous infarct lesions, net water uptake was determined by direct measurement of the volumetric difference between the ischemic and normal hemisphere and was correlated with net water uptake calculated by ischemic density measurements. RESULTS: With regard to in vitro data, water uptake by density measurement was equivalent to direct volumetric measurement (r = 0.99, P < 0.0001; mean ± SD difference, -0.29% ± 0.39%, not different from 0, P < 0.0001). In the study cohort, the mean ± SD uptake of water within infarct measured by volumetry was 44.7 ± 26.8 mL and the mean percent water uptake per lesion volume was 22.7% ± 7.4%. This was equivalent to percent water uptake obtained from density measurements: 21.4% ± 6.4%. The mean difference between percent water uptake by direct volumetry and percent water uptake by CT density was -1.79% ± 3.40%, which was not significantly different from 0 (P < 0.0001). CONCLUSIONS: Volume of water uptake in infarct lesions can be calculated quantitatively by relative CT density measurements. Voxel-wise imaging of water uptake depicts lesion pathophysiology and could serve as a quantitative imaging biomarker of acute infarct lesions.

The use of multiparametric quantitative magnetic resonance imaging for evaluating visually assigned lesion groups in patients with multiple sclerosis.

In multiple sclerosis (MS), inflammatory lesions present a broad spectrum of histopathologic processes. For a better discrimination, lesions are visually defined into different lesion groups according to their appearance on conventional magnetic resonance imaging (MRI). The aim of this study was to investigate the properties of different MS lesion groups using multiparametric quantitative MRI. 35 patients diagnosed with relapsing-remitting MS received 3 Tesla MRI including magnetization-prepared 2 rapid acquisition gradient echo, diffusion tensor imaging and magnetization transfer imaging. Lesion segmentation was performed for T2 lesions, black holes and contrast-enhancing lesions. A subtraction mask was created including only T2 lesions that did not correspond to a black hole or contrast-enhancing lesion. T1 relaxation time (T1-RT), magnetization transfer ratio (MTR), mean diffusivity (MD) and fractional anisotropy (FA) were determined for every lesion and in normal-appearing white matter. Only MD differed significantly between all lesion groups and NAWM (p < 0.05), while FA differed between all lesion groups but not NAWM. T1-RT and MTR were not useful imaging biomarkers to distinguish between lesion groups. A lack of sensitivity and specificity and unproportional alterations of quantitative MRI measures, due to heterogenous histopathologic processes within lesions, may be a possible explanation for missing discrimination. Thus, not only interpretation of visually defined MS lesion but also interpretation of quantitative MRI measures remains challenging and should be conducted carefully.

Transit time homogenization in ischemic stroke - A novel biomarker of penumbral microvascular failure?

Cerebral ischemia causes widespread capillary no-flow in animal studies. The extent of microvascular impairment in human stroke, however, is unclear. We examined how acute intra-voxel transit time characteristics and subsequent recanalization affect tissue outcome on follow-up MRI in a historic cohort of 126 acute ischemic stroke patients. Based on perfusion-weighted MRI data, we characterized voxel-wise transit times in terms of their mean transit time (MTT), standard deviation (capillary transit time heterogeneity - CTH), and the CTH:MTT ratio (relative transit time heterogeneity), which is expected to remain constant during changes in perfusion pressure in a microvasculature consisting of passive, compliant vessels. To aid data interpretation, we also developed a computational model that relates graded microvascular failure to changes in these parameters. In perfusion-diffusion mismatch tissue, prolonged mean transit time (>5 seconds) and very low cerebral blood flow (≤6 mL/100 mL/min) was associated with high risk of infarction, largely independent of recanalization status. In the remaining mismatch region, low relative transit time heterogeneity predicted subsequent infarction if recanalization was not achieved. Our model suggested that transit time homogenization represents capillary no-flow. Consistent with this notion, low relative transit time heterogeneity values were associated with lower cerebral blood volume. We speculate that low RTH may represent a novel biomarker of penumbral microvascular failure.

Comprehensive analysis of early fractional anisotropy changes in acute ischemic stroke.

BACKGROUND AND PURPOSE: Cerebral ischemia leads to a rapid decrease of the apparent diffusion coefficient. For fractional anisotropy both increase and decrease have been reported in acute ischemic stroke. Aim of this study was to characterize early water diffusion changes in a homogenous group of acute stroke patients and to clarify the issue of early fractional anisotropy changes and their relation to time from symptom onset. METHODS: MRI data of patients with acute ischemic stroke examined by diffusion tensor imaging within 8h after symptom were analyzed. We calculated fractional anisotropy, eigenvalues and the isotropic and anisotropic components of the diffusion tensor. The values were calculated as ratios between the ischemic lesion and a mirror region in the unaffected side and correlated with clinical parameters. RESULTS: We included 63 patients: 49% female, mean age 69 ± 14 years, median NIHSS on admission 9 (IQR 4-14). For the whole sample, mean fractional anisotropy was increased (ratio: 1.083 ± 0.168), while all other diffusion parameters were decreased. Both the isotropic and anisotropic component of the diffusion tensor were decreased with a more pronounced decrease of the isotropic component (ratios: isotropic = 0.730 ± 0.106, anisotropic = 0.788 ± 0.127; p<0.001). There was no correlation of fractional anisotropy with time from symptom onset. Looking at individual patients, fractional anisotropy was increased in 70%. There were no differences in clinical characteristics between patients with increased and decreased fractional anisotropy. CONCLUSION: Fractional anisotropy increase in acute stroke results from a more pronounced decrease of the isotropic diffusion component and is not related to time from symptom onset. Thus, fractional anisotropy is not helpful as a surrogate marker of lesion age in the very first hours of stroke.

T1w dark blood imaging improves detection of contrast enhancing lesions in multiple sclerosis.

PURPOSE: In multiple sclerosis (MS) the sensitivity for detection of contrast enhancing lesions (CEL) in T1-weighted scans is essential for diagnostics and therapy decisions. The purpose of our study was to evaluate the sensitivity of T1w MPRAGE scans in comparison to T1w dark blood technique (T1-DB) for CEL in MS. MATERIALS AND METHODS: 3T MR imaging was performed in 37 MS patients, including T2-weighted imaging, T1w MPRAGE before and after gadolinium injection (unenhanced-T1 and T1-CE) and T1-DB imaging. After gadolinium application, the T1-DB scan was performed prior to T1-CE. From unenhanced-T1 and T1-CE scans, subtraction images (T1-SUB) were calculated. The number of CEL was determined separately on T1-CE and T1-DB by two raters independently. Lesions only detected on T1-DB scans then were verified on T1-SUB. Only lesions detected by both raters were included in further analysis. RESULTS: In 16 patients, at least one CEL was detected by both rater, either on T1-CE or T1-DB. All lesions that were detected on T1-CE were also detected on T1-DB images. The total number of contrast enhancing lesions detected on T1-DB images (n = 54) by both raters was significantly higher than the corresponding number of lesions identified on T1-CE (n = 27) (p = 0.01); all of these lesions could be verified on SUB images. In 21 patients, no CEL was detected in any of the sequences. CONCLUSIONS: The application of T1-DB technique increases the sensitivity for CEL in MS, especially for those lesions that show only subtle increase in intensity after Gadolinium application but remain hypo- or iso-intense to surrounding tissue.

Reduced rich-club connectivity is related to disability in primary progressive MS.

OBJECTIVE: To investigate whether the structural connectivity of the brain's rich-club organization is altered in patients with primary progressive MS and whether such changes to this fundamental network feature are associated with disability measures. METHODS: We recruited 37 patients with primary progressive MS and 21 healthy controls for an observational cohort study. Structural connectomes were reconstructed based on diffusion-weighted imaging data using probabilistic tractography and analyzed with graph theory. RESULTS: We observed the same topological organization of brain networks in patients and controls. Consistent with the originally defined rich-club regions, we identified superior frontal, precuneus, superior parietal, and insular cortex in both hemispheres as rich-club nodes. Connectivity within the rich club was significantly reduced in patients with MS (p = 0.039). The extent of reduced rich-club connectivity correlated with clinical measurements of mobility (Kendall rank correlation coefficient τ = -0.20, p = 0.047), hand function (τ = -0.26, p = 0.014), and information processing speed (τ = -0.20, p = 0.049). CONCLUSIONS: In patients with primary progressive MS, the fundamental organization of the structural connectome in rich-club and peripheral nodes was preserved and did not differ from healthy controls. The proportion of rich-club connections was altered and correlated with disability measures. Thus, the rich-club organization of the brain may be a promising network phenotype for understanding the patterns and mechanisms of neurodegeneration in MS.

Subtypes of primary angiitis of the CNS identified by MRI patterns reflect the size of affected vessels.

OBJECTIVE: To describe patterns of diagnostic findings, and identify subgroups of primary angiitis of the central nervous system (PACNS). METHODS: We retrospectively analysed 31 patients with PACNS. Cases were selected by predetermined diagnostic criteria and stratified into biopsy-proven and imaging-based PACNS. We compared clinical characteristics, cerebrospinal fluid (CSF) findings and imaging results including high-resolution vessel wall MRI between groups. RESULTS: There were 31 cases of PACNS (mean age 45.6 years, 58.1% female), of whom 17 (55%) were biopsy-proven, 14 (45%) were based on imaging findings. Patients with a positive biopsy had fewer infarcts (29.4% vs 85.7%, p=0.003), were more likely to have meningeal and parenchymal contrast enhancement (76.5% vs 28.6%, p=0.012), were less likely to have abnormal MR angiography (11.8% vs 100%, p<0.001) and did not show vessel wall enhancement at the time of diagnosis (0% vs 76.9%, p<0.001). In contrast, patients with imaging-based diagnosis showed more frequently multiple infarcts and vessel abnormalities, with vessel wall enhancement in most of the cases. Clinical characteristics and CSF analysis did not reveal marked differences between groups. INTERPRETATION: Multi-parametric MRI distinguishes two subtypes of PACNS that most likely differ concerning the affected vessel size. Biopsy-proven PACNS primarily involves smaller vessels beyond the resolution of vascular imaging, while imaging-based PACNS affects predominantly medium-sized vessels leading to false-negative biopsy results. Using distinct MRI patterns may be helpful for selecting patients for appropriate invasive diagnostic modalities.

ERic Acute StrokE Recanalization: A study using predictive analytics to assess a new device for mechanical thrombectomy.

Aim and hypothesis Using a new study design, we investigate whether next-generation mechanical thrombectomy devices improve clinical outcomes in ischemic stroke patients. We hypothesize that this new methodology is superior to intravenous tissue plasminogen activator therapy alone. Methods and design ERic Acute StrokE Recanalization is an investigator-initiated prospective single-arm, multicenter, controlled, open label study to compare the safety and effectiveness of a new recanalization device and distal access catheter in acute ischemic stroke patients with symptoms attributable to acute ischemic stroke and vessel occlusion of the internal cerebral artery or middle cerebral artery. Study outcome The primary effectiveness endpoint is the volume of saved tissue. Volume of saved tissue is defined as difference of the actual infarct volume and the brain volume that is predicted to develop infarction by using an optimized high-level machine learning model that is trained on data from a historical cohort treated with IV tissue plasminogen activator. Sample size estimates Based on own preliminary data, 45 patients fulfilling all inclusion criteria need to complete the study to show an efficacy >38% with a power of 80% and a one-sided alpha error risk of 0.05 (based on a one sample t-test). Discussion ERic Acute StrokE Recanalization is the first prospective study in interventional stroke therapy to use predictive analytics as primary and secondary endpoint. Such trial design cannot replace randomized controlled trials with clinical endpoints. However, ERic Acute StrokE Recanalization could serve as an exemplary trial design for evaluating nonpivotal neurovascular interventions.

CT-perfusion stroke imaging: a threshold free probabilistic approach to predict infarct volume compared to traditional ischemic thresholds.

The aim was to evaluate a novel method of threshold-free prediction of brain infarct from computed tomography perfusion (CTP) imaging in comparison to conventional ischemic thresholds. In a multicenter cohort of 161 patients with acute large vessel occlusion who received endovascular therapy, brain infarction was predicted by CTP using (1) optimized parameter cut-off values determined by ROC curve analysis and (2) probabilistic logistic regression threshold-free analysis. Predicted infarct volumes and prediction errors based on four perfusion parameter maps were compared against observed infarcts. In 93 patients with successful recanalization, the mean observed infarct volume was 35.7 ± 61.9 ml (the reference for core infarct not savable by reperfusion). Optimal parameter thresholds predicted mean infarct volumes between 53.2 ± 44.4 and 125.0 ± 95.4 ml whereas threshold-free analysis predicted mean volumes between 35.9 ± 28.5 and 36.1 ± 29.0 ml. In 68 patients with persistent occlusion, the mean observed infarct volume was 113.4 ± 138.3 ml (the reference to define penumbral infarct savable by reperfusion). Predicted mean infarct volumes by parameter thresholds ranged from 91.4 ± 81.5 to 163.8 ± 135.7 ml, by threshold-free analysis from 113.2 ± 89.9 to 113.5 ± 89.0 ml. Threshold-free prediction of infarct volumes had a higher precision and lower patient-specific prediction error than conventional thresholding. Penumbra to core lesion mismatch estimate may therefore benefit from threshold-free CTP analysis.

Edema is not a reliable diagnostic sign to exclude small brain metastases.

No prior systematic study on the extent of vasogenic edema (VE) in patients with brain metastases (BM) exists. Here, we aim to determine 1) the general volumetric relationship between BM and VE, 2) a threshold diameter above which a BM shows VE, and 3) the influence of the primary tumor and location of the BM in order to improve diagnostic processes and understanding of edema formation. This single center, retrospective study includes 173 untreated patients with histologically proven BM. Semi-manual segmentation of 1416 BM on contrast-enhanced T1-weighted images and of 865 VE on fluid-attenuated inversion recovery/T2-weighted images was conducted. Statistical analyses were performed using a paired-samples t-test, linear regression/generalized mixed-effects model, and receiver-operating characteristic (ROC) curve controlling for the possible effect of non-uniformly distributed metastases among patients. For BM with non-confluent edema (n = 545), there was a statistically significant positive correlation between the volumes of the BM and the VE (P < 0.001). The optimal threshold for edema formation was a diameter of 9.4 mm for all BM. The primary tumors as interaction term in multivariate analysis had a significant influence on VE formation whereas location had not. Hence VE development is dependent on the volume of the underlying BM and the site of the primary neoplasm, but not from the location of the BM.

Reliability of cortical lesion detection on double inversion recovery MRI applying the MAGNIMS-Criteria in multiple sclerosis patients within a 16-months period.

PURPOSE: In patients with multiple sclerosis (MS), Double Inversion Recovery (DIR) magnetic resonance imaging (MRI) can be used to identify cortical lesions (CL). We sought to evaluate the reliability of CL detection on DIR longitudinally at multiple subsequent time-points applying the MAGNIMs scoring criteria for CLs. METHODS: 26 MS patients received a 3T-MRI (Siemens, Skyra) with DIR at 12 time-points (TP) within a 16 months period. Scans were assessed in random order by two different raters. Both raters separately marked all CLs on each scan and total lesion numbers were obtained for each scan-TP and patient. After a retrospective re-evaluation, the number of consensus CLs (conL) was defined as the total number of CLs, which both raters finally agreed on. CLs volumes, relative signal intensities and CLs localizations were determined. Both ratings (conL vs. non-consensus scoring) were compared for further analysis. RESULTS: A total number of n = 334 CLs were identified by both raters in 26 MS patients with a first agreement of both raters on 160 out of 334 of the CLs found (κ = 0.48). After the retrospective re-evaluation, consensus agreement increased to 233 out of 334 CL (κ = 0.69). 93.8% of conL were visible in at least 2 consecutive TP. 74.7% of the conL were visible in all 12 consecutive TP. ConL had greater mean lesion volumes and higher mean signal intensities compared to lesions that were only detected by one of the raters (p<0.05). A higher number of CLs in the frontal, parietal, temporal and occipital lobe were identified by both raters than the number of those only identified by one of the raters (p<0.05). CONCLUSIONS: After a first assessment, slightly less than a half of the CL were considered as reliably detectable on longitudinal DIR images. A retrospective re-evaluation notably increased the consensus agreement. However, this finding is narrowed, considering the fact that retrospective evaluation steps might not be practicable in clinical routine. Lesions that were not reliably identifiable by both raters seem to be characterized by lower signal intensity and smaller size, or located in distinct anatomical brain regions.