András Jakab

The Multimodal Brain Tumor Image Segmentation Benchmark (BRATS)

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients - manually annotated by up to four raters - and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.

Connectivity-based parcellation reveals interhemispheric differences in the insula

The aim of this work was to use probabilistic diffusion tractography to examine the organization of the human insular cortex based on the similarities of its remote projections. Forty right-handed healthy subjects (33.8xa0±xa012.7xa0years old) with no history of neurological injury were included in the study. After the spatial standardization of diffusion tensor images, insular cortical masks were delineated based on the Harvard–Oxford Cortical Atlas and were used to initiate fibertracking. Cluster analysis by the k-means algorithm was employed to partition the insular voxels into two groups that featured the most distinct distribution of connections. In order to perform volumetric comparisons, the assigned label maps were transformed back to space of the subjects’ native anatomical MR images. The outlines of the change in connectivity profile did not respect the known cytoarchitectural subdivisions and were shown to be independent from the gyral anatomy. Interhemispheric asymmetry in the volumes of connectivity-based subdivisions was observed putatively marking a leftward functional dominance of the anterior insula and its reciprocally interconnected targets which influences the size of insular area where similar connections are represented. The fractional anisotropy values were not significantly different between the hemipsheres or connectivity-based clusters; however, the mean diffusivity was higher in the anterior insula in both hemispheres.

Cell therapy for human ischemic heart diseases: Critical review and summary of the clinical experiences

A decade ago, stem or progenitor cells held the promise of tissue regeneration in human myocardium, with the expectation that these therapies could rescue ischemic myocyte damage, enhance vascular density and rebuild injured myocardium. The accumulated evidence in 2014 indicates, however, that the therapeutic success of these cells is modest and the tissue regeneration involves much more complex processes than cell-related biologics. As the quest for the ideal cell or combination of cells continues, alternative cell types, such as resident cardiac cells, adipose-derived or phenotypic modified stem or progenitor cells have also been applied, with the objective of increasing both the number and the retention of the reparative cells in the myocardium. Two main delivery routes (intracoronary and percutaneous intramyocardial) of stem cells are currently used preferably for patients with recent acute myocardial infarction or ischemic cardiomyopathy. Other delivery modes, such as surgical or intravenous via peripheral veins or coronary sinus have also been utilized with less success. Due to the difficult recruitment of patients within conceivable timeframe into cardiac regenerative trials, meta-analyses of human cardiac cell-based studies have tried to gather sufficient number of subjects to present a statistical compelling statement, reporting modest success with a mean increase of 0.9-6.1% in left ventricular global ejection fraction. Additionally, nearly half of the long-term studies reported the disappearance of the initial benefit of this treatment. Beside further extensive efforts to increase the efficacy of currently available methods, pre-clinical experiments using new techniques such as tissue engineering or exploiting paracrine effect hold promise to regenerate injured human cardiac tissue.

MIDA: A Multimodal Imaging-Based Detailed Anatomical Model of the Human Head and Neck

Computational modeling and simulations are increasingly being used to complement experimental testing for analysis of safety and efficacy of medical devices. Multiple voxel- and surface-based whole- and partial-body models have been proposed in the literature, typically with spatial resolution in the range of 1–2 mm and with 10–50 different tissue types resolved. We have developed a multimodal imaging-based detailed anatomical model of the human head and neck, named “MIDA”. The model was obtained by integrating three different magnetic resonance imaging (MRI) modalities, the parameters of which were tailored to enhance the signals of specific tissues: i) structural T1- and T2-weighted MRIs; a specific heavily T2-weighted MRI slab with high nerve contrast optimized to enhance the structures of the ear and eye; ii) magnetic resonance angiography (MRA) data to image the vasculature, and iii) diffusion tensor imaging (DTI) to obtain information on anisotropy and fiber orientation. The unique multimodal high-resolution approach allowed resolving 153 structures, including several distinct muscles, bones and skull layers, arteries and veins, nerves, as well as salivary glands. The model offers also a detailed characterization of eyes, ears, and deep brain structures. A special automatic atlas-based segmentation procedure was adopted to include a detailed map of the nuclei of the thalamus and midbrain into the head model. The suitability of the model to simulations involving different numerical methods, discretization approaches, as well as DTI-based tensorial electrical conductivity, was examined in a case-study, in which the electric field was generated by transcranial alternating current stimulation. The voxel- and the surface-based versions of the models are freely available to the scientific community.

Glioma grade assessment by using histogram analysis of diffusion tensor imaging-derived maps

IntroductionCurrent endeavors in neuro-oncology include morphological validation of imaging methods by histology, including molecular and immunohistochemical techniques. Diffusion tensor imaging (DTI) is an up-to-date methodology of intracranial diagnostics that has gained importance in studies of neoplasia. Our aim was to assess the feasibility of discriminant analysis applied to histograms of preoperative diffusion tensor imaging-derived images for the prediction of glioma grade validated by histomorphology.MethodsTumors of 40 consecutive patients included 13 grade II astrocytomas, seven oligoastrocytomas, six grade II oligodendrogliomas, three grade III oligoastrocytomas, and 11 glioblastoma multiformes. Preoperative DTI data comprised: unweighted (B0) images, fractional anisotropy, longitudinal and radial diffusivity maps, directionally averaged diffusion-weighted imaging, and trace images. Sampling consisted of generating histograms for gross tumor volumes; 25 histogram bins per scalar map were calculated. The histogram bins that allowed the most precise determination of low-grade (LG) or high-grade (HG) classification were selected by multivariate discriminant analysis. Accuracy of the model was defined by the success rate of the leave-one-out cross-validation.ResultsStatistical descriptors of voxel value distribution did not differ between LG and HG tumors and did not allow classification. The histogram model had 88.5% specificity and 85.7% sensitivity in the separation of LG and HG gliomas; specificity was improved when cases with oligodendroglial components were omitted.ConclusionConstructing histograms of preoperative radiological images over the tumor volume allows representation of the grade and enables discrimination of LG and HG gliomas which has been confirmed by histopathology.

Generation of Individualized Thalamus Target Maps by Using Statistical Shape Models and Thalamocortical Tractography

BACKGROUND AND PURPOSE: Neurosurgical interventions of the thalamus rely on transferring stereotactic coordinates from an atlas onto the patients MR brain images. We propose a prototype application for performing thalamus target map individualization by fusing patient-specific thalamus geometric information and diffusion tensor tractography. MATERIALS AND METHODS: Previously, our workgroup developed a thalamus atlas by fusing anatomic information from 7 histologically processed thalami. Thalamocortical connectivity maps were generated from DTI scans of 40 subjects by using a previously described procedure and were mapped to a standard neuroimaging space. These data were merged into a statistical shape model describing the morphologic variability of the thalamic outline, nuclei, and connectivity landmarks. This model was used to deform the atlas to individual images. Postmortem MR imaging scans were used to quantify the accuracy of nuclei predictions. RESULTS: Reliable tractography-based markers were located in the ventral lateral thalamus, with the somatosensory connections coinciding with the VPLa and VPLp nuclei; and motor/premotor connections, with the VLpv and VLa nuclei. Prediction accuracy of thalamus outlines was higher with the SSM approach than the ACPC alignment of data (0.56 mm versus 1.24; Dice overlap: 0.87 versus 0.7); for individual nuclei: 0.65 mm, Dice: 0.63 (SSM); 1.24 mm, Dice: 0.4 (ACPC). CONCLUSIONS: Previous studies have already applied DTI to the thalamus. As a further step in this direction, we demonstrate a hybrid approach by using statistical shape models, which have the potential to cope with intersubject variations in individual thalamus geometry.

Autistic traits in neurotypical adults: correlates of graph theoretical functional network topology and white matter anisotropy patterns.

Attempts to explicate the neural abnormalities behind autism spectrum disorders frequently revealed impaired brain connectivity, yet our knowledge is limited about the alterations linked with autistic traits in the non-clinical population. In our study, we aimed at exploring the neural correlates of dimensional autistic traits using a dual approach of diffusion tensor imaging (DTI) and graph theoretical analysis of resting state functional MRI data. Subjects were sampled from a public neuroimaging dataset of healthy volunteers. Inclusion criteria were adult age (age: 18–65), availability of DTI and resting state functional acquisitions and psychological evaluation including the Social Responsiveness Scale (SRS) and Autistic Spectrum Screening Questionnaire (ASSQ). The final subject cohort consisted of 127 neurotypicals. Global brain network structure was described by graph theoretical parameters: global and average local efficiency. Regional topology was characterized by degree and efficiency. We provided measurements for diffusion anisotropy. The association between autistic traits and the neuroimaging findings was studied using a general linear model analysis, controlling for the effects of age, gender and IQ profile. Significant negative correlation was found between the degree and efficiency of the right posterior cingulate cortex and autistic traits, measured by the combination of ASSQ and SRS scores. Autistic phenotype was associated with the decrease of whole-brain local efficiency. Reduction of diffusion anisotropy was found bilaterally in the temporal fusiform and parahippocampal gyri. Numerous models describe the autistic brain connectome to be dominated by reduced long-range connections and excessive short-range fibers. Our finding of decreased efficiency supports this hypothesis although the only prominent effect was seen in the posterior limbic lobe, which is known to act as a connector hub. The neural correlates of the autistic trait in neurotypicals showed only limited similarities to the reported findings in clinical populations with low functioning autism.

Mapping changes of in vivo connectivity patterns in the human mediodorsal thalamus: correlations with higher cognitive and executive functions.

The mediodorsal thalamic nucleus is recognized as an association hub mediating interconnections with mainly the prefrontal cortex. Tracer studies in primates and in vivo diffusion tensor tractography findings in both humans and monkeys confirm its role in relaying networks that connect to the dorsolateral prefrontal, orbitofrontal, frontal medial and cingulate cortex. Our study was designed to use in vivo probabilistic tractography to describe the pathways emerging from or projecting to the mediodorsal nucleus; moreover, to use such information to automatically define subdivisions based on the divergence of remote structural connections. Diffusion tensor MR imaging data of 156 subjects were utilized to perform connectivity-based segmentation of the mediodorsal nucleus by employing a k-means clustering algorithm. Two domains were revealed (medial and lateral) that are separated from each other by a sagittally oriented plane. For each subject, general assessment of cognitive performance by means of the Wechsler Abbreviated Scale of Intelligence and measures of Delis-Kaplan Executive Function System (D-KEFS) test was utilized. Inter-subject variability in terms of connectivity-based cluster sizes was discovered and the relative sizes of the lateral mediodorsal domain correlated with the individuals’ performance in the D-KEFS Sorting test (ru2009=u20090.232, pu2009=u20090.004). Our results show that the connectivity-based parcellation technique applied to the mediodorsal thalamic nucleus delivers a single subject level descriptor of connectional topography; furthermore, we revealed a possible weak interaction between executive performance and the size of the thalamic area from which pathways converge to the lateral prefrontal cortex.

Time Course of Endothelium-Dependent and -Independent Coronary Vasomotor Response to Coronary Balloons and Stents : Comparison of Plain and Drug-Eluting Balloons and Stents

OBJECTIVESnThis study sought to determine the time dependency of the endothelium-dependent and -independent vascular responses after percutaneous coronary intervention (PCI) with drug-eluting (DEB) or plain balloons, bare-metal (BMS), and drug-eluting (DES) stents, or controls.nnnBACKGROUNDnLong-term endothelial dysfunction after DES implantation is associated with delayed healing and late thrombosis.nnnMETHODSnDomestic pigs underwent PCI using DEB or plain balloon, BMS, or DES. The dilated and stented segments, and the proximal reference segments of stents and control arteries were explanted at 5-h, 24-h, 1-week, and 1-month follow-up (FUP). Endothelin-induced vasoconstriction and endothelium-dependent and -independent vasodilation of the arterial segments were determined in vitro and were related to histological results.nnnRESULTSnDES- and BMS-treated arteries showed proneness to vasoconstriction 5 h post-PCI. The endothelium-dependent vasodilation was profoundly (p < 0.05) impaired early after PCI (9.8 ± 3.7%, 13.4 ± 9.2%, 5.7 ± 5.3%, and 7.6 ± 4.7% using plain balloon, DEB, BMS, and DES, respectively), as compared with controls (49.6 ± 9.5%), with slow recovery. In contrast to DES, the endothelium-related vasodilation of vessels treated with plain balloon, DEB, and BMS was increased at 1 month, suggesting enhanced endogenous nitric oxide production of the neointima. The endothelium-independent (vascular smooth muscle-related) vasodilation decreased significantly at 1 day, with slow normalization during FUP. All PCI-treated vessels exhibited imbalance between vasoconstriction-vasodilation, which was more pronounced in DES- and BMS-treated vessels. No correlation between histological parameters and vasomotor function was found, indicating complex interactions between the healing neoendothelium and smooth muscle post-PCI.nnnCONCLUSIONSnCoronary arteries treated with plain balloon, DEB, BMS, and DES showed time-dependent loss of endothelial-dependent and -independent vasomotor function, with imbalanced contraction/dilation capacity.

Secretome of apoptotic peripheral blood cells (APOSEC) attenuates microvascular obstruction in a porcine closed chest reperfused acute myocardial infarction model: role of platelet aggregation and vasodilation.

Although epicardial blood flow can be restored by an early intervention in most cases, a lack of adequate reperfusion at the microvascular level is often a limiting prognostic factor of acute myocardial infarction (AMI). Our group has recently found that paracrine factors secreted from apoptotic peripheral blood mononuclear cells (APOSEC) attenuate the extent of myocardial injury. The aim of this study was to determine the influence of APOSEC on microvascular obstruction (MVO) in a porcine AMI model. A single dose of APOSEC was intravenously injected in a closed chest reperfused infarction model. MVO was determined by magnetic resonance imaging and cardiac catheterization. Role of platelet function and vasodilation were monitored by means of ELISA, flow cytometry, aggregometry, western blot and myographic experiments in vitro and in vivo. Treatment of AMI with APOSEC resulted in a significant reduction of MVO. Platelet activation markers were reduced in plasma samples obtained during AMI, suggesting an anti-aggregatory capacity of APOSEC. This finding was confirmed by in vitro tests showing that activation and aggregation of both porcine and human platelets were significantly impaired by co-incubation with APOSEC, paralleled by vasodilator-stimulated phosphoprotein (VASP)-mediated inhibition of platelets. In addition, APOSEC evidenced a significant vasodilatory capacity on coronary arteries via p-eNOS and iNOS activation. Our data give first evidence that APOSEC reduces the extent of MVO during AMI, and suggest that modulation of platelet activation and vasodilation in the initial phase after myocardial infarction contributes to the improved long-term outcome in APOSEC treated animals.