76 research outputs found

    Complex rearranged small supernumerary marker chromosomes (sSMC), three new cases; evidence for an underestimated entity?

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    <p>Abstract</p> <p>Background</p> <p>Small supernumerary marker chromosomes (sSMC) are present ~2.6 × 10<sup>6 </sup>human worldwide. sSMC are a heterogeneous group of derivative chromosomes concerning their clinical consequences as well as their chromosomal origin and shape. Besides the sSMC present in Emanuel syndrome, i.e. der(22)t(11;22)(q23;q11), only few so-called complex sSMC are reported.</p> <p>Results</p> <p>Here we report three new cases of unique complex sSMC. One was a <it>de novo </it>case with a dic(13 or 21;22) and two were maternally derived: a der(18)t(8;18) and a der(13 or 21)t(13 or 21;18). Thus, in summary, now 22 cases of unique complex sSMC are available in the literature. However, this special kind of sSMC might be under-diagnosed among sSMC-carriers.</p> <p>Conclusion</p> <p>More comprehensive characterization of sSMC and approaches like reverse fluorescence in situ hybridization (FISH) or array based comparative genomic hybridization (array-CGH) might identify them to be more frequent than only ~0.9% among all sSMC.</p

    Amide Proton Transfer Contrast Distribution in Different Brain Regions in Young Healthy Subjects

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    ObjectivesTo define normal signal intensity values of amide proton transfer-weighted (APTw) magnetic resonance (MR) imaging in different brain regions.Materials and MethodsTwenty healthy subjects (9 females, mean age 29 years, range 19 – 37 years) underwent MR imaging at 3 Tesla. 3D APTw (RF saturation B1,rms = 2 μT, duration 2 s, 100% duty cycle) and 2D T2-weighted turbo spin echo (TSE) images were acquired. Postprocessing (image fusion, ROI measurements of APTw intensity values in 22 different brain regions) was performed and controlled by two independent neuroradiologists. Values were measured separately for each brain hemisphere. A subject was scanned both in prone and supine position to investigate differences between hemispheres. A mixed model on a 5% significance level was used to assess the effect of gender, brain region and side on APTw intensity values.ResultsMean APTw intensity values in the hippocampus and amygdala varied between 1.13 and 1.57%, in the deep subcortical nuclei (putamen, globus pallidus, head of caudate nucleus, thalamus, red nucleus, substantia nigra) between 0.73 and 1.84%, in the frontal, occipital and parietal cortex between 0.56 and 1.03%; in the insular cortex between 1.11 and 1.15%, in the temporal cortex between 1.22 and 1.37%, in the frontal, occipital and parietal white matter between 0.32 and 0.54% and in the temporal white matter between 0.83 and 0.89%. APTw intensity values were significantly impacted both by brain region (p &lt; 0.001) and by side (p &lt; 0.001), whereby overall values on the left side were higher than on the right side (1.13 vs. 0.9%). Gender did not significantly impact APTw intensity values (p = 0.24). APTw intensity values between the left and the right side were partially reversed after changing the position of one subject from supine to prone.ConclusionWe determined normal baseline APTw intensity values in different anatomical localizations in healthy subjects. APTw intensity values differed both between anatomical regions and between left and right brain hemisphere

    Sex and age dependencies of aqueductal cerebrospinal fluid dynamics parameters in healthy subjects

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    Objectives: To assess the influence of age and sex on 10 cerebrospinal fluid (CSF) flow dynamics parameters measured with an MR phase contrast (PC) sequence within the cerebral aqueduct at the level of the intercollicular sulcus.Materials and Methods: 128 healthy subjects (66 female subjects with a mean age of 52.9 years and 62 male subjects with a mean age of 51.8 years) with a normal Evans index, normal medial temporal atrophy (MTA) score, and without known disorders of the CSF circulation were included in the study. A PC MR sequence on a 3T MR scanner was used. Ten different flow parameters were analyzed using postprocessing software. Ordinal and linear regression models were calculated.Results: The parameters stroke volume (sex: p < 0.001, age: p = 0.003), forward flow volume (sex: p < 0.001, age: p = 0.002), backward flow volume (sex: p < 0.001, age: p = 0.018), absolute stroke volume (sex: p < 0.001, age: p = 0.005), mean flux (sex: p < 0.001, age: p = 0.001), peak velocity (sex: p = 0.009, age: p = 0.0016), and peak pressure gradient (sex: p = 0.029, age: p = 0.028) are significantly influenced by sex and age. The parameters regurgitant fraction, stroke distance, and mean velocity are not significantly influenced by sex and age.Conclusion: CSF flow dynamics parameters measured in the cerebral aqueduct are partly age and sex dependent. For establishment of reliable reference values for clinical use in future studies, the impact of sex and age should be considered and incorporated

    Characterization of Novel Antimalarial Compound ACT-451840: Preclinical Assessment of Activity and Dose-Efficacy Modeling.

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    BACKGROUND: Artemisinin resistance observed in Southeast Asia threatens the continued use of artemisinin-based combination therapy in endemic countries. Additionally, the diversity of chemical mode of action in the global portfolio of marketed antimalarials is extremely limited. Addressing the urgent need for the development of new antimalarials, a chemical class of potent antimalarial compounds with a novel mode of action was recently identified. Herein, the preclinical characterization of one of these compounds, ACT-451840, conducted in partnership with academic and industrial groups is presented. METHOD AND FINDINGS: The properties of ACT-451840 are described, including its spectrum of activities against multiple life cycle stages of the human malaria parasite Plasmodium falciparum (asexual and sexual) and Plasmodium vivax (asexual) as well as oral in vivo efficacies in two murine malaria models that permit infection with the human and the rodent parasites P. falciparum and Plasmodium berghei, respectively. In vitro, ACT-451840 showed a 50% inhibition concentration of 0.4 nM (standard deviation [SD]: ± 0.0 nM) against the drug-sensitive P. falciparum NF54 strain. The 90% effective doses in the in vivo efficacy models were 3.7 mg/kg against P. falciparum (95% confidence interval: 3.3-4.9 mg/kg) and 13 mg/kg against P. berghei (95% confidence interval: 11-16 mg/kg). ACT-451840 potently prevented male gamete formation from the gametocyte stage with a 50% inhibition concentration of 5.89 nM (SD: ± 1.80 nM) and dose-dependently blocked oocyst development in the mosquito with a 50% inhibitory concentration of 30 nM (range: 23-39). The compound's preclinical safety profile is presented and is in line with the published results of the first-in-man study in healthy male participants, in whom ACT-451840 was well tolerated. Pharmacokinetic/pharmacodynamic (PK/PD) modeling was applied using efficacy in the murine models (defined either as antimalarial activity or as survival) in relation to area under the concentration versus time curve (AUC), maximum observed plasma concentration (Cmax), and time above a threshold concentration. The determination of the dose-efficacy relationship of ACT-451840 under curative conditions in rodent malaria models allowed prediction of the human efficacious exposure. CONCLUSION: The dual activity of ACT-451840 against asexual and sexual stages of P. falciparum and the activity on P. vivax have the potential to meet the specific profile of a target compound that could replace the fast-acting artemisinin component and harbor additional gametocytocidal activity and, thereby, transmission-blocking properties. The fast parasite reduction ratio (PRR) and gametocytocidal effect of ACT-451840 were recently also confirmed in a clinical proof-of-concept (POC) study

    Consensus guidelines for the definition of time-to-event end points in image-guided tumor ablation: results of the SIO and DATECAN initiative

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    International audienceThere is currently no consensus regarding preferred clinical outcome measures following image-guided tumor ablation or clear definitions of oncologic end points. This consensus document proposes standardized definitions for a broad range of oncologic outcome measures with recommendations on how to uniformly document, analyze, and report outcomes. The initiative was coordinated by the Society of Interventional Oncology in collaboration with the Definition for the Assessment of Time-to-Event End Points in Cancer Trials, or DATECAN, group. According to predefined criteria, based on experience with clinical trials, an international panel of 62 experts convened. Recommendations were developed using the validated three-step modified Delphi consensus method. Consensus was reached on when to assess outcomes per patient, per session, or per tumor; on starting and ending time and survival time definitions; and on time-to-event end points. Although no consensus was reached on the preferred classification system to report complications, quality of life, and health economics issues, the panel did agree on using the most recent version of a validated patient-reported outcome questionnaire. This article provides a framework of key opinion leader recommendations with the intent to facilitate a clear interpretation of results and standardize worldwide communication. Widespread adoption will improve reproducibility, allow for accurate comparisons, and avoid misinterpretations in the field of interventional oncology research. Published under a CC BY 4.0 license. Online supplemental material is available for this article. See also the editorial by Liddell in this issue

    Ultrafast Intracranial Vessel Imaging With Non-Cartesian Spiral 3-Dimensional Time-of-Flight Magnetic Resonance Angiography at 1.5 T: An In Vitro and Clinical Study in Healthy Volunteers

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    OBJECTIVES Non-Cartesian spiral magnetic resonance (MR) acquisition may enable higher scan speeds, as the spiral traverses the k-space more efficiently per given time than in Cartesian trajectories. Spiral MR imaging can be implemented in time-of-flight (TOF) MR angiography (MRA) sequences. In this study, we tested the performance of five 3-dimensional TOF MRA sequences for intracranial vessel imaging at 1.5 T with qualitative and quantitative image quality metrics based on in vitro and in vivo measurements. Specifically, 3 novel spiral TOF MRA sequences (spiral-TOFs) and a compressed sensing (CS) technology-accelerated TOF MRA sequence (CS 3.5) were compared with a conventional (criterion standard) parallel imaging-accelerated TOF MRA sequence (SENSE). MATERIALS AND METHODS The SENSE sequence (5:08 minutes) was compared with the CS 3.5 sequence (3:06 minutes) and a spiral-TOF (spiral, 1:32 minutes), all with identical resolutions. In addition, 2 further isotropic spiral-TOFs (spiral 0.8, 2:12 minutes; spiral 0.6, 5:22 minutes) with higher resolution were compared with the SENSE. First, vessel tracking experiments were performed in vitro with a dedicated vascular phantom to determine possible differences in the depiction of cross-sectional areas of vessel segments. For the in vitro tests, an additional 3-dimensional proton density-weighted sequence was added for comparison reasons. Second, 3 readers blinded to sequence details assessed qualitative (16 features) and 2 readers assessed quantitative (contrast-to-noise ratio [CNR], contrast ratio [CR], vessel sharpness, and full width at half maximum edge criterion measurements) image quality based on images acquired from scanning 10 healthy volunteers with all 5 TOF sequences. Scores from quantitative image quality analysis were compared with Kruskal-Wallis, analysis of variance, or Welch's analysis of variance, followed by Dunnett's or Dunnett's T3 post hoc tests. Scores from qualitative image quality analysis were compared with exact binomial tests, and the level of interreader agreement was determined with Krippendorff's alpha. RESULTS Concerning the in vitro tests, there were no significant differences between the 5 TOFs and the proton density-weighted sequence in measuring cross-sectional areas of vessel segments (P = 0.904). As for the in vivo tests, the CS 3.5 exhibited equal qualitative image quality as the SENSE, whereas the 3 spiral-TOFs outperformed the SENSE in several categories (P values from 0.002 to 0.031). Specifically, the spiral 0.8 and 0.6 sequences achieved significantly higher scores in 12 categories. Interreader agreement ranged from poor (alpha = -0.013, visualization of internal carotid artery segment C7) to substantial (alpha = 0.737, number of vessels visible, sagittal). As for the quantitative metrics, the CS 3.5 and all 3 spiral-TOFs presented with significantly worse CNR than the SENSE ([mean ± SD] SENSE 37.48 ± 7.13 vs CS 3.5 31.14 ± 5.97 vs spiral 19.77 ± 1.65 vs spiral 0.8 16.18 ± 2.14 vs spiral 0.6 10.37 ± 1.05). The CR values did not differ significantly between the SENSE and the other TOFs except for the spiral sequence that showed significantly improved CR (SENSE 0.53 ± 0.03 vs spiral 0.56 ± 0.03). As for vessel sharpness, the SENSE was outperformed by all spiral-TOFs (SENSE 0.37 ± 0.03 vs spiral 0.52 ± 0.07 vs spiral 0.8 0.53 ± 0.08 vs spiral 0.6 0.73 ± 0.09), whereas the CS 3.5 performed equally well (SENSE 0.37 ± 0.03 vs CS 3.5 0.37 ± 0.03). Full width at half maximum values did not differ significantly between any TOF. CONCLUSIONS Spiral-TOFs may deliver high-quality intracranial vessel imaging thus matching the performance of conventional parallel imaging-accelerated TOFs (such as the SENSE). Specifically, imaging can be performed at unprecedented scan times as short as 1:32 minutes per sequence (70.12% scan time reduction compared with SENSE). Optionally, spiral imaging may also be used to increase spatial resolution while maintaining the scan time of a Cartesian-based acquisition schema. The CNR was decreased in spiral-TOF images

    Common artefacts encountered on images acquired with combined compressed sensing and SENSE

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    Abstract Various techniques have been proposed which aim at scan time reduction and/or at improved image quality by increasing the spatial resolution. Compressed sensing (CS) takes advantage of the fact that MR images are usually sparse in some transform domains and recovers this sparse representation from undersampled data. CS may be combined with parallel imaging such as sensitivity encoding (SENSE), hereafter referred to as Compressed SENSE, to further accelerate image acquisition since both techniques rely on different ancillary information. In practice, Compressed SENSE may reduce scan times of two-dimensional (2D) and three-dimensional (3D) scans by up to 50% depending on the sequence acquired and it works on 1.5-T or 3-T scanners. Compressed SENSE may be applied to 2D and 3D sequences in various anatomies and image contrasts. Image artefacts (i.e. motion, metal and flow artefacts, susceptibility artefacts) frequently appear on magnetic resonance images. The Compressed SENSE technique may cause special artefacts, which might influence image assessment if they go undetected by imaging readers. Our institution has been using Compressed SENSE for over half a year, both in a neuroradiological setting and for musculoskeletal examinations. So far, three special image artefacts—called the wax-layer artefact, the streaky-linear artefact and the starry-sky artefact—have been encountered and we aim to review these main artefacts appearing in sequences acquired with Compressed SENSE. Teaching Points • Compressed SENSE combines compressed sensing and SENSE technique. • Compressed SENSE permits scan time reduction and increases spatial image resolution. • Images acquired with Compressed SENSE may present with special artefacts. • Knowledge of artefacts is necessary for reliable image assessment

    Amide Proton Transfer Contrast Distribution in Different Brain Regions in Young Healthy Subjects

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    Objectives: To define normal signal intensity values of amide proton transfer-weighted (APTw) magnetic resonance (MR) imaging in different brain regions. Materials and Methods: Twenty healthy subjects (9 females, mean age 29 years, range 19 – 37 years) underwent MR imaging at 3 Tesla. 3D APTw (RF saturation B1,rms = 2 μT, duration 2 s, 100% duty cycle) and 2D T2-weighted turbo spin echo (TSE) images were acquired. Postprocessing (image fusion, ROI measurements of APTw intensity values in 22 different brain regions) was performed and controlled by two independent neuroradiologists. Values were measured separately for each brain hemisphere. A subject was scanned both in prone and supine position to investigate differences between hemispheres. A mixed model on a 5% significance level was used to assess the effect of gender, brain region and side on APTw intensity values. Results: Mean APTw intensity values in the hippocampus and amygdala varied between 1.13 and 1.57%, in the deep subcortical nuclei (putamen, globus pallidus, head of caudate nucleus, thalamus, red nucleus, substantia nigra) between 0.73 and 1.84%, in the frontal, occipital and parietal cortex between 0.56 and 1.03%; in the insular cortex between 1.11 and 1.15%, in the temporal cortex between 1.22 and 1.37%, in the frontal, occipital and parietal white matter between 0.32 and 0.54% and in the temporal white matter between 0.83 and 0.89%. APTw intensity values were significantly impacted both by brain region (p < 0.001) and by side (p < 0.001), whereby overall values on the left side were higher than on the right side (1.13 vs. 0.9%). Gender did not significantly impact APTw intensity values (p = 0.24). APTw intensity values between the left and the right side were partially reversed after changing the position of one subject from supine to prone. Conclusion: We determined normal baseline APTw intensity values in different anatomical localizations in healthy subjects. APTw intensity values differed both between anatomical regions and between left and right brain hemisphere

    Intraneural hemorrhage in traumatic oculomotor nerve palsy

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    Isolated traumatic oculomotor nerve palsy without internal ophthalmoplegia is a rare condition after closed head trauma. The nerve strain leads to intraneural edema with nerve swelling on T2-weighted magnetic resonance (MR) images and traumatic disruption of the blood peripheral nerve barrier with contrast enhancement on T1-weighted MR images. In this patient, susceptibility-weighted MR imaging allowed the direct visualization of the intraneural hemorrhage after suspected traumatic diffuse neuronal axonal injury
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