Machine learning assisted DSC-MRI radiomics as a tool for glioma classification by grade and mutation status

BACKGROUND: Combining MRI techniques with machine learning methodology is rapidly gaining attention as a promising method for staging of brain gliomas. This study assesses the diagnostic value of such a framework applied to dynamic susceptibility contrast (DSC)-MRI in classifying treatment-naïve gliomas from a multi-center patients into WHO grades II-IV and across their isocitrate dehydrogenase (IDH) mutation status. METHODS: Three hundred thirty-three patients from 6 tertiary centres, diagnosed histologically and molecularly with primary gliomas (IDH-mutant = 151 or IDH-wildtype = 182) were retrospectively identified. Raw DSC-MRI data was post-processed for normalised leakage-corrected relative cerebral blood volume (rCBV) maps. Shape, intensity distribution (histogram) and rotational invariant Haralick texture features over the tumour mask were extracted. Differences in extracted features across glioma grades and mutation status were tested using the Wilcoxon two-sample test. A random-forest algorithm was employed (2-fold cross-validation, 250 repeats) to predict grades or mutation status using the extracted features. RESULTS: Shape, distribution and texture features showed significant differences across mutation status. WHO grade II-III differentiation was mostly driven by shape features while texture and intensity feature were more relevant for the III-IV separation. Increased number of features became significant when differentiating grades further apart from one another. Gliomas were correctly stratified by mutation status in 71% and by grade in 53% of the cases (87% of the gliomas grades predicted with distance less than 1). CONCLUSIONS: Despite large heterogeneity in the multi-center dataset, machine learning assisted DSC-MRI radiomics hold potential to address the inherent variability and presents a promising approach for non-invasive glioma molecular subtyping and grading

Focal and Generalized Patterns of Cerebral Cortical Veins Due to Non-Convulsive Status Epilepticus or Prolonged Seizure Episode after Convulsive Status Epilepticus – A MRI Study Using Susceptibility Weighted Imaging

OBJECTIVE The aim of this study was to investigate variant patterns of cortical venous oxygenation during status epilepticus (SE) using susceptibility-weighted imaging (SWI). METHODS We analyzed magnetic resonance imaging (MRI) scans of 26 patients with clinically witnessed prolonged seizures and/or EEG-confirmed SE. All MRI exams encompassed SWI, dynamic susceptibility contrast perfusion MRI (MRI-DSC) and diffusion-weighted imaging (DWI). We aimed to identify distinct patterns of SWI signal alterations that revealed regional or global increases of cerebral blood flow (CBF) and DWI restrictions. We hypothesized that SWI-related oxygenation patterns reflect ictal or postictal patterns that resemble SE or sequelae of seizures. RESULTS Sixteen patients were examined during nonconvulsive status epilepticus (NCSE) as confirmed by EEG, a further ten patients suffered from witnessed and prolonged seizure episode ahead of imaging without initial EEG. MRI patterns of 15 of the 26 patients revealed generalized hyperoxygenation by SWI in keeping with either global or multifocal cortical hyperperfusion. Eight patients revealed a focal hyperoxygenation pattern related to focal CBF increase and three patients showed a focal deoxygenation pattern related to focal CBF decrease. CONCLUSIONS SWI-related hyper- and deoxygenation patterns resemble ictal and postictal CBF changes within a range from globally increased to focally decreased perfusion. In all 26 patients the SWI patterns were in keeping with ictal hyperperfusion (hyperoxygenation patterns) or postictal hypoperfusion (deoxygenation patterns) respectively. A new finding of this study is that cortical venous patterns in SWI can be not only focally, but globally attenuated. SWI may thus be considered as an alternative contrast-free MR sequence to identify perfusion changes related to ictal or postictal conditions

Tolerance and effects of FK506 (tacrolimus) on nerve regeneration: a pilot study.

In adults, the outcome of nerve suture and nerve autograft remains generally unsatisfactory. FK506 (tacrolimus), an immunosuppressant drug used in transplantation, has been reported in animal studies to enhance nerve regeneration. In hand transplantation patients, nerve regeneration was unexpectedly good and rapid, and this observation has been attributed to FK506. The present Phase II experiment investigated the tolerance to FK506 after nerve suture or autograft, and the potential effects of the drug on axonal regeneration. Following strict criteria, five patients were included in this study. Within 7 days of nerve repair (median, ulnar and sciatic transections), patients received FK506 (aiming for blood concentrations between 5 and 8 ng/ml) for a total duration of 60 days. The patients were carefully followed with clinical and biological monitoring in order to detect side-effects. A clinical and electrophysiological assessment of the effect of FK506 on nerve regeneration was conducted. No undesirable side-effect was observed during or after FK506 treatment, but one non-compliant patient discontinued treatment. There was no evident improvement of sensory, motor or functional recovery at the end of the follow-up period (average duration 39.8 months), as compared to the expected clinical result without treatment. Although statistically non-significant, FK506 seemed to accelerate the progression of the Hoffmann-Tinel sign, but without impact on the final result.Clinical Trial, Phase IIJournal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Middle cerebral artery revascularization: anatomical studies and considerations on the anastomosis site Revascularização da artéria cerebral média: estudo anatômico e considerações sobre o local de sutura

In the surgical management of skull base lesions and vascular diseases such as giant aneurysms, involvement of the internal carotid artery may require the resection or the occlusion of the vessel. The anastomosis of the external carotid artery and the middle cerebral artery with venous graft may be indicated to re-establish the blood flow. To determine the best suture site in the middle cerebral artery, an anatomical study was carried out. Fourteen cerebral hemispheres were analysed after the injection of red latex into the internal carotid artery. The superior and inferior trunk of the main division of the middle cerebral artery have more than 2 mm of diameter. They are superficial allowing an anastomosis using a venous graft. The superior trunk has a disadvantage, it gives rise to branches for the precentral and post-central giri. The anastomosis with the inferior trunk presents lower risk of neurological deficit even though the angular artery originates from it.<br>No tratamento cirúrgico das lesões da base do crânio e patologias vasculares como aneurismas gigantes, a ressecção ou oclusão da artéria carótida interna pode ser necessária. A anastomose das artérias carótida externa e cerebral média com interposição de enxerto venoso pode ser utilizada para restabelecer o fluxo sangüíneo. Para determinar o melhor local de sutura na artéria cerebral média, realizou-se um estudo anatômico. Quatorze hemisférios cerebrais foram analisados depois da injeção de látex vermelho na artéria carótida interna. Os ramos superior e inferior da divisão principal da artéria cerebral média têm mais de 2 mm de diâmetro. Eles são superficiais e permitem uma anastomose utilizando um enxerto venoso. O tronco superior tem a desvantagem de dar origem aos ramos para os giros pré e pós-centrais. A anastomose com o tronca inferior apresenta menor risco de déficit neurológico, apesar da artéria angular ter origem desse vaso

Persistence and activation of malaria hypnozoites in long-term primary hepatocyte cultures

Comment in: Malarial liver parasites awaken in culture. Barnwell JW, Galinski MR. Nat Med. 2014 Mar;20(3):237-9. doi: 10.1038/nm.3498. PMID: 24603792International audienceMalaria relapses, resulting from the activation of quiescent hepatic hypnozoites of Plasmodium vivax and Plasmodium ovale, hinder global efforts to control and eliminate malaria. As primaquine, the only drug capable of eliminating hypnozoites, is unsuitable for mass administration, an alternative drug is needed urgently. Currently, analyses of hypnozoites, including screening of compounds that would eliminate them, can only be made using common macaque models, principally Macaca rhesus and Macaca fascicularis, experimentally infected with the relapsing Plasmodium cynomolgi. Here, we present a protocol for long-term in vitro cultivation of P. cynomolgi-infected M. fascicularis primary hepatocytes during which hypnozoites persist and activate to resume normal development. In a proof-of-concept experiment, we obtained evidence that exposure to an inhibitor of histone modification enzymes implicated in epigenetic control of gene expression induces an accelerated rate of hypnozoite activation. The protocol presented may further enable investigations of hypnozoite biology and the search for compounds that kill hypnozoites or disrupt their quiescence