Three patients had severe ataxia and memory impairment in a phase 1 trial of a fatty acid amide hydrolase inhibitor designed as an analgesic and antiinflammatory drug. One patient became brain dead. ...MRI of the brain showed lesions in the pons and hippocampi.
A decrease in fatty acid amide hydrolase (FAAH) activity increases the levels of endogenous analogues of cannabinoids, or endocannabinoids.
1
FAAH inhibitors have shown analgesic and antiinflammatory activity in animal models,
2
and some have been tested for these purposes in phase 1 and phase 2 studies.
3
Phase 3 studies were not pursued owing to a lack of efficacy. BIA 10-2474, with the chemical name 3-(1-(cyclohexyl(methyl)carbamoyl)-1H-imidazol-4-yl)pyridine 1-oxide, is a new reversible FAAH inhibitor. A phase 1 study was conducted in healthy volunteers to explore the safety profile of BIA 10-2474. Five of the six participants who had received the highest cumulative dose . . .
OBJECTIVETo describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.
METHODSIn ...this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.
RESULTSThe cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20–92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imagingthe former less frequently had acute respiratory distress syndrome (p = 0.006) and more frequently had corticospinal tract signs (p = 0.02). Patients with encephalitis were younger (p = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement (p = 0.009).
CONCLUSIONSPatients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.
CLINICALTRIALS.GOV IDENTIFIERNCT04368390.
The characterization of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral kinetics in hospitalized patients and its association with mortality is unknown. We analyzed death and ...nasopharyngeal viral kinetics in 655 hospitalized patients from the prospective French COVID cohort. The model predicted a median peak viral load that coincided with symptom onset. Patients with age ≥65 y had a smaller loss rate of infected cells, leading to a delayed median time to viral clearance occurring 16 d after symptom onset as compared to 13 d in younger patients (
< 10
). In multivariate analysis, the risk factors associated with mortality were age ≥65 y, male gender, and presence of chronic pulmonary disease (hazard ratio HR > 2.0). Using a joint model, viral dynamics after hospital admission was an independent predictor of mortality (HR = 1.31,
< 10
). Finally, we used our model to simulate the effects of effective pharmacological interventions on time to viral clearance and mortality. A treatment able to reduce viral production by 90% upon hospital admission would shorten the time to viral clearance by 2.0 and 2.9 d in patients of age <65 y and ≥65 y, respectively. Assuming that the association between viral dynamics and mortality would remain similar to that observed in our population, this could translate into a reduction of mortality from 19 to 14% in patients of age ≥65 y with risk factors. Our results show that viral dynamics is associated with mortality in hospitalized patients. Strategies aiming to reduce viral load could have an effect on mortality rate in this population.
MRI plays a crucial role in multiple sclerosis diagnostic and patient follow-up. In particular, the delineation of T2-FLAIR hyperintense lesions is crucial although mostly performed manually - a ...tedious task. Many methods have thus been proposed to automate this task. However, sufficiently large datasets with a thorough expert manual segmentation are still lacking to evaluate these methods. We present a unique dataset for MS lesions segmentation evaluation. It consists of 53 patients acquired on 4 different scanners with a harmonized protocol. Hyperintense lesions on FLAIR were manually delineated on each patient by 7 experts with control on T2 sequence, and gathered in a consensus segmentation for evaluation. We provide raw and preprocessed data and a split of the dataset into training and testing data, the latter including data from a scanner not present in the training dataset. We strongly believe that this dataset will become a reference in MS lesions segmentation evaluation, allowing to evaluate many aspects: evaluation of performance on unseen scanner, comparison to individual experts performance, comparison to other challengers who already used this dataset, etc.
•Smoking is more frequent in patients with ruptured aneurysms.•Elevated blood pressure is more frequent in patients with ruptured aneurysms.•Aneurysm characteristics associated with rupture are size, ...location, and neck size.
Identifying patients with intracranial aneurysms (IA) who have a high risk of rupture is critical to determine optimal management. ARETA (Analysis of Recanalization after Endovascular Treatment of intracranial Aneurysm) is a prospective, multicenter study, dedicated to evaluating endovascular treatment of IA. We aimed to identify factors associated with ruptured status, using this very large series of patients with ruptured and unruptured aneurysms.
Several analyses were conducted in the ARETA population: univariate and multivariate analyses in the whole population of patients and aneurysms to determine patient and aneurysm factors associated with aneurysm rupture, as well as a matched pair analysis (based on aneurysm size) conducted in the subgroup of patients with only one aneurysm to analyze the patient and aneurysm factors simultaneously.
From December 2013 to May 2015, 1289 patients with 1761 aneurysms were included in ARETA. The multivariate analysis identified four patient factors: elevated blood pressure (EBP), no familial history, single IA, and active smoking, and four aneurysm factors: size≥5mm, narrow neck, irregular shape, and ACA/Acom location, associated with rupture status. In the matched pair analysis, five risk factors of rupture were identified: no familial history of aneurysm, narrow neck, active smoking, ACA/Acom location, and irregular shape.
The most important patient factors associated with IA rupture are smoking and EBP. Given that size is a well-identified aneurysm factor, narrow neck also seems to be associated with aneurysm rupture. Further studies are needed to confirm this factor and determine underlying mechanisms. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01942512.
Purpose
To demonstrate that fluid and white matter suppression (FLAWS) imaging can be used for high‐resolution T1 mapping with low transmitted bias field (B1+) sensitivity at 7T.
Methods
The FLAWS ...sequence was optimized for 0.8‐mm isotropic resolution imaging. The theoretical accuracy and precision of the FLAWS T1 mapping was compared with the one of the magnetization‐prepared two rapid gradient echoes (MP2RAGE) sequence optimized for low B1+ sensitivity. FLAWS images were acquired at 7T on six healthy volunteers (21 to 48 years old; two women). MP2RAGE and saturation‐prepared with two rapid gradient echoes (SA2RAGE) datasets were also acquired to obtain T1 mapping references and B1+ maps. The contrast‐to‐noise ratio (CNR) between brain tissues was measured in the FLAWS‐hco and MP2RAGE‐uni images. The Pearson correlation was measured between the MP2RAGE and FLAWS T1 maps. The effect of B1+ on FLAWS T1 mapping was assessed using the Pearson correlation.
Results
The FLAWS‐hco images were characterized by a higher brain tissue CNR (CNRWM/GM=5.5, CNRWM/CSF=14.7, CNRGM/CSF=10.3) than the MP2RAGE‐uni images (CNRWM/GM=4.9, CNRWM/CSF=6.6, CNRGM/CSF=3.7). The theoretical accuracy and precision of the FLAWS T1 mapping (acc=91.9%;prec=90.2%) were in agreement with those provided by the MP2RAGE T1 mapping (acc=90.0%;prec=86.8%). A good agreement was found between in vivo T1 values measured with the MP2RAGE and FLAWS sequences (r = 0.91). A weak correlation was found between the FLAWS T1 map and the B1+ map within cortical gray matter and white matter segmentations (rWM=‐0.026; rGM=0.081).
Conclusion
The results from this study suggest that FLAWS is a good candidate for high‐resolution T1‐weighted imaging and T1 mapping at the field strength of 7T.
We present a study of multiple sclerosis segmentation algorithms conducted at the international MICCAI 2016 challenge. This challenge was operated using a new open-science computing infrastructure. ...This allowed for the automatic and independent evaluation of a large range of algorithms in a fair and completely automatic manner. This computing infrastructure was used to evaluate thirteen methods of MS lesions segmentation, exploring a broad range of state-of-theart algorithms, against a high-quality database of 53 MS cases coming from four centers following a common definition of the acquisition protocol. Each case was annotated manually by an unprecedented number of seven different experts. Results of the challenge highlighted that automatic algorithms, including the recent machine learning methods (random forests, deep learning, …), are still trailing human expertise on both detection and delineation criteria. In addition, we demonstrate that computing a statistically robust consensus of the algorithms performs closer to human expertise on one score (segmentation) although still trailing on detection scores.
Arterial spin labeling is a magnetic resonance perfusion imaging technique that, while providing results comparable to methods currently considered as more standard concerning the quantification of ...the cerebral blood flow, is subject to limitations related to its low signal-to-noise ratio and low resolution. In this work, we investigate the relevance of using a non-local patch-based super-resolution method driven by a high resolution structural image to increase the level of details in arterial spin labeling images. This method is evaluated by comparison with other image dimension increasing techniques on a simulated dataset, on images of healthy subjects and on images of subjects scanned for brain tumors, who had a dynamic susceptibility contrast acquisition. The influence of an increase of ASL images resolution on partial volume effects is also investigated in this work.
•Super-resolution for arterial spin labeling magnetic resonance images is validated.•Validation on simulations, healthy subjects and dynamic susceptibility contrast.•High resolution reconstructed images are closer to reference images.•Super-resolution reduces partial volume effects in cerebral blood flow images.
In this paper, we introduce a new locally multivariate procedure to quantitatively extract voxel-wise patterns of abnormal perfusion in individual patients. This a contrario approach uses a ...multivariate metric from the computer vision community that is suitable to detect abnormalities even in the presence of closeby hypo- and hyper-perfusions. This method takes into account local information without applying Gaussian smoothing to the data. Furthermore, to improve on the standard a contrario approach, which assumes white noise, we introduce an updated a contrario approach that takes into account the spatial coherency of the noise in the probability estimation.
Validation is undertaken on a dataset of 25 patients diagnosed with brain tumours and 61 healthy volunteers. We show how the a contrario approach outperforms the massively univariate general linear model usually employed for this type of analysis.
Purpose
To test the reproducibility and accuracy of pharmacokinetic parameter measurements on five analysis software packages (SPs) for dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI), ...using simulated and clinical data.
Materials and Methods
This retrospective study was Institutional Review Board‐approved. Simulated tissues consisted of pixel clusters of calculated dynamic signal changes for combinations of Tofts model pharmacokinetic parameters (volume transfer constant Ktrans, extravascular extracellular volume fraction ve), longitudinal relaxation time (T1). The clinical group comprised 27 patients treated for rectal cancer, with 36 3T DCE‐MR scans performed between November 2012 and February 2014, including dual‐flip‐angle T1 mapping and a dynamic postcontrast T1‐weighted, 3D spoiled gradient‐echo sequence. The clinical and simulated images were postprocessed with five SPs to measure Ktrans, ve, and the initial area under the gadolinium curve (iAUGC). Modified Bland–Altman analysis was conducted, intraclass correlation coefficients (ICCs) and within‐subject coefficients of variation were calculated.
Results
Thirty‐one examinations from 23 patients were of sufficient technical quality and postprocessed. Measurement errors were observed on the simulated data for all the pharmacokinetic parameters and SPs, with a bias ranging from −0.19 min−1 to 0.09 min−1 for Ktrans, −0.15 to 0.01 for ve, and −0.65 to 1.66 mmol.L−1.min for iAUGC. The ICC between SPs revealed moderate agreement for the simulated data (Ktrans: 0.50; ve: 0.67; iAUGC: 0.77) and very poor agreement for the clinical data (Ktrans: 0.10; ve: 0.16; iAUGC: 0.21).
Conclusion
Significant errors were found in the calculated DCE‐MRI pharmacokinetic parameters for the perfusion analysis SPs, resulting in poor inter‐software reproducibility. J. Magn. Reson. Imaging 2016;43:1288–1300.
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