Automatic C-Plane Detection in Pelvic Floor Transperineal Volumetric Ultrasound

Transperineal volumetric ultrasound (US) imaging has become routine practice for diagnosing pelvic floor disease (PFD). Hereto, clinical guidelines stipulate to make measurements in an anatomically defined 2D plane within a 3D volume, the so-called C-plane. This task is currently performed manually in clinical practice, which is labour-intensive and requires expert knowledge of pelvic floor anatomy, as no computer-aided C-plane method exists. To automate this process, we propose a novel, guideline-driven approach for automatic detection of the C-plane. The method uses a convolutional neural network (CNN) to identify extreme coordinates of the symphysis pubis and levator ani muscle (which define the C-plane) directly via landmark regression. The C-plane is identified in a postprocessing step. When evaluated on 100 US volumes, our best performing method (multi-task regression with UNet) achieved a mean error of 6.05 mm and 4.81 ∘ and took 20 s. Two experts blindly evaluated the quality of the automatically detected planes and manually defined the (gold standard) C-plane in terms of their clinical diagnostic quality. We show that the proposed method performs comparably to the manual definition. The automatic method reduces the average time to detect the C-plane by 100 s and reduces the need for high-level expertise in PFD US assessment

Feature- versus rule-based generalization in rats, pigeons and humans

Humans can spontaneously create rules that allow them to efficiently generalize what they have learned to novel situations. An enduring question is whether rule-based generalization is uniquely human or whether other animals can also abstract rules and apply them to novel situations. In recent years, there have been a number of high-profile claims that animals such as rats can learn rules. Most of those claims are quite weak because it is possible to demonstrate that simple associative systems (which do not learn rules) can account for the behavior in those tasks. Using a procedure that allows us to clearly distinguish feature-based from rule-based generalization (the Shanks-Darby procedure), we demonstrate that adult humans show rule-based generalization in this task, while generalization in rats and pigeons was based on featural overlap between stimuli. In brief, when learning that a stimulus made of two components ("AB") predicts a different outcome than its elements ("A" and "B"), people spontaneously abstract an opposites rule and apply it to new stimuli (e.g., knowing that "C" and "D" predict one outcome, they will predict that "CD" predicts the opposite outcome). Rats and pigeons show the reverse behavior-they generalize what they have learned, but on the basis of similarity (e.g., "CD" is similar to "C" and "D", so the same outcome is predicted for the compound stimulus as for the components). Genuinely rule-based behavior is observed in humans, but not in rats and pigeons, in the current procedure

Fully Automatic 3D-TEE Segmentation for the Planning of Transcatheter Aortic Valve Implantation

A novel fully automatic framework for aortic valve (AV) trunk segmentation in three-dimensional (3-D) transesophageal echocardiography (TEE) datasets is proposed. The methodology combines a previously presented semiautomatic segmentation strategy by using shape-based B-spline Explicit Active Surfaces with two novel algorithms to automate the quantification of relevant AV measures. The first combines a fast rotation-invariant 3-D generalized Hough transform with a vessel-like dark tube detector to initialize the segmentation. After segmenting the AV wall, the second algorithm focuses on aligning this surface with the reference ones in order to estimate the short-axis (SAx) planes (at the left ventricular outflow tract, annulus, sinuses of Valsalva, and sinotubular junction) in which to perform the measurements. The framework has been tested in 20 3-D-TEE datasets with both stenotic and nonstenotic AVs. The initialization algorithm presented a median error of around 3 mm for the AV axis endpoints, with an overall feasibility of 90%. In its turn, the SAx detection algorithm showed to be highly reproducible, with indistinguishable results compared with the variability found between the experts' defined planes. Automatically extracted measures at the four levels showed a good agreement with the experts' ones, with limits of agreement similar to the interobserver variability. Moreover, a validation set of 20 additional stenotic AV datasets corroborated the method's applicability and accuracy. The proposed approach mitigates the variability associated with the manual quantification while significantly reducing the required analysis time (12 s versus 5 to 10 min), which shows its appeal for automatic dimensioning of the AV morphology in 3-D-TEE for the planning of transcatheter AV implantation.This work was supported by the project "ON.2 SR&TD Integrated Program (Norte-07-0124-FEDER-000017)" cofunded by the Programa Operacional Regional do Norte (ON.2- O Novo Norte), Quadro de Referencia Estrategico Nacional, through Fundo Europeu de Desenvolvimento Regional. The work of S. Queiros and P. Morais was supported by the FCT-Fundacao para a Ciencia e a Tecnologia and the European Social Found through the Programa Operacional Capital Humano in the scope of the Ph.D. Grants SFRH/BD/93443/2013 and SFRH/BD/95438/2013, respectively. J. L. Vilaca and J. D'hooge are joint last authors. Asterisk indicates corresponding author.info:eu-repo/semantics/publishedVersio

Deep neural network-based clustering of deformation curves reveals novel disease features in PLN pathogenic variant carriers

Echocardiographic deformation curves provide detailed information on myocardial function. Deep neural networks (DNNs) may enable automated detection of disease features in deformation curves, and improve the clinical assessment of these curves. We aimed to investigate whether an explainable DNN-based pipeline can be used to detect and visualize disease features in echocardiographic deformation curves of phospholamban (PLN) p.Arg14del variant carriers. A DNN was trained to discriminate PLN variant carriers (n = 278) from control subjects (n = 621) using raw deformation curves obtained by 2D-speckle tracking in the longitudinal axis. A visualization technique was used to identify the parts of these curves that were used by the DNN for classification. The PLN variant carriers were clustered according to the output of the visualization technique. The DNN showed excellent discriminatory performance (C-statistic 0.93 [95% CI 0.87–0.97]). We identified four clusters with PLN-associated disease features in the deformation curves. Two clusters showed previously described features: apical post-systolic shortening and reduced systolic strain. The two other clusters revealed novel features, both reflecting delayed relaxation. Additionally, a fifth cluster was identified containing variant carriers without disease features in the deformation curves, who were classified as controls by the DNN. This latter cluster had a very benign disease course regarding development of ventricular arrhythmias. Applying an explainable DNN-based pipeline to myocardial deformation curves enables automated detection and visualization of disease features. In PLN variant carriers, we discovered novel disease features which may improve individual risk stratification. Applying this approach to other diseases will further expand our knowledge on disease-specific deformation patterns. Graphical abstract: [Figure not available: see fulltext.] Overview of the deep neural network-based pipeline for feature detection in myocardial deformation curves. Firstly, phospholamban (PLN) p.Arg14del variant carriers and controls were selected and a deep neural network (DNN) was trained to detect the PLN variant carriers. Subsequently, a clustering-based approach was performed on the attention maps of the DNN, which revealed 4 distinct phenotypes of PLN variant carriers with different prognoses. Moreover, a cluster without features and a benign prognosis was detected

IFNβ Protects Neurons from Damage in a Murine Model of HIV-1 Associated Brain Injury.

Infection with human immunodeficiency virus-1 (HIV-1) causes brain injury. Type I interferons (IFNα/β) are critical mediators of any anti-viral immune response and IFNβ has been implicated in the temporary control of lentiviral infection in the brain. Here we show that transgenic mice expressing HIV-1 envelope glycoprotein 120 in their central nervous system (HIVgp120tg) mount a transient IFNβ response and provide evidence that IFNβ confers neuronal protection against HIVgp120 toxicity. In cerebrocortical cell cultures, neuroprotection by IFNβ against gp120 toxicity is dependent on IFNα receptor 1 (IFNAR1) and the β-chemokine CCL4, as IFNAR1 deficiency and neutralizing antibodies against CCL4, respectively, abolish the neuroprotective effects. We find in vivo that IFNβ mRNA is significantly increased in HIVgp120tg brains at 1.5, but not 3 or 6 months of age. However, a four-week intranasal IFNβ treatment of HIVgp120tg mice starting at 3.5 months of age increases expression of CCL4 and concomitantly protects neuronal dendrites and pre-synaptic terminals in cortex and hippocampus from gp120-induced damage. Moreover, in vivo and in vitro data suggests astrocytes are a major source of IFNβ-induced CCL4. Altogether, our results suggest exogenous IFNβ as a neuroprotective factor that has potential to ameliorate in vivo HIVgp120-induced brain injury

Heart Rate Variability and Atria Function in Children at Late Follow-Up Evaluation After Atrioventricular Node Slow-Pathway Radiofrequency Ablation

This study was designed to assess the changes in the conductive system, autonomic dysfunction, and global and regional function of the atria and ventricles in children late after slow-pathway radiofrequency ablation (RFA). The study enrolled 22 children, who has successfully undergone RFA 2 to 5 years previously (RFA group) and 20 healthy children (control group). Electrophysiologic study was performed for the RFA group. Holter monitoring and echocardiography were performed for all the children. At a late follow-up assessment, the RFA children were free of paroxysms, whereas 8 of the 22 children (36%) reported transient palpitations. Both mean and maximal heart rates (HR) were significantly increased, whereas indices of HR variability (% of succesive normal sinus RR intervals exceeding 50 ms [pNN50], root mean square of the succesive normal sinus RR interval difference [rMSSD], high-frequency component [HFC]) were significantly decreased in the RFA group compared with preablation and control data. Left atrial (LA) and right atrial (RA) volumes were significantly higher, and atria deformation indices were significantly lower in the RFA group. Correlations were found between the mean HR and the volumes of LA (r = 0.477; p < 0.001) and RA (r = 0.512; p < 0.001). A negative correlation between the maximal LA volume and the longitudinal strain rate (SR) during relaxation (r = –0.476; p = 0.03) and a positive correlation between the minimal LA volume and both longitudinal SR (r = 0.361; p = 0.03) and strain (ε) (r = 0.375; p = 0.024) during contraction were shown. These data suggest a possible link between atrial dysfunction and the hyperadrenergic state after RFA

What is new in uremic toxicity?

Uremic syndrome results from a malfunctioning of various organ systems due to the retention of compounds which, under normal conditions, would be excreted into the urine and/or metabolized by the kidneys. If these compounds are biologically active, they are called uremic toxins. One of the more important toxic effects of such compounds is cardio-vascular damage. A convenient classification based on the physico-chemical characteristics affecting the removal of such compounds by dialysis is: (1) small water-soluble compounds; (2) protein-bound compounds; (3) the larger “middle molecules”. Recent developments include the identification of several newly detected compounds linked to toxicity or the identification of as yet unidentified toxic effects of known compounds: the dinucleotide polyphosphates, structural variants of angiotensin II, interleukin-18, p-cresylsulfate and the guanidines. Toxic effects seem to be typically exerted by molecules which are “difficult to remove by dialysis”. Therefore, dialysis strategies have been adapted by applying membranes with larger pore size (high-flux membranes) and/or convection (on-line hemodiafiltration). The results of recent studies suggest that these strategies have better outcomes, thereby clinically corroborating the importance attributed in bench studies to these “difficult to remove” molecules

Regulation of Motor Function and Behavior by Atypical Chemokine Receptor 1

The final publication is available at Springer via http://dx.doi.org/10.1007/s10519-014-9665-7Atypical Chemokine Receptor 1 (ACKR1), previously known as the Duffy Antigen Receptor for Chemokines, stands out among chemokine receptors for its high selective expression on Purkinje cells of the cerebellum, consistent with the ability of ACKR1 ligands to activate Purkinje cells in vitro. Nevertheless, evidence for ACKR1 regulation of brain function in vivo has been lacking. Here we demonstrate that Ackr1−/− mice have markedly impaired balance and ataxia when placed on a rotating rod and increased tremor when injected with harmaline, a drug that induces whole-body tremor by activating Purkinje cells. Ackr1−/− mice also exhibited impaired exploratory behavior, increased anxiety-like behavior and frequent episodes of marked hypoactivity under low-stress conditions. The behavioral phenotype of Ackr1−/− mice was the opposite of the phenotype occurring in mice with cerebellar degeneration and the defects persisted when Ackr1 was deficient only on non-hematopoietic cells. We conclude that normal motor function and behavior depend in part on negative regulation of Purkinje cell activity by Ackr1

Morphological, physiological and behavioural evaluation of a ‘Mice in Space’ housing system

Environmental conditions likely affect physiology and behaviour of mice used for life sciences research on Earth or in Space. Here, we analysed the effects of cage confinement on the weightbearing musculoskeletal system, behaviour and stress of wild-type mice (C57BL/6JRj, 30 g b.wt., total n = 24) housed for 25 days in a prototypical ground-based and fully automated life support habitat device called “Mice in Space” (MIS). Compared with control housing (individually ventilated cages) the MIS mice revealed no significant changes in soleus muscle size and myofiber distribution (type I vs. II) and quality of bone (3-D microarchitecture and mineralisation of calvaria, spine and femur) determined by confocal and micro-computed tomography. Corticosterone metabolism measured non-invasively (faeces) monitored elevated adrenocortical activity at only start of the MIS cage confinement (day 1). Behavioural tests (i.e., grip strength, rotarod, L/D box, elevated plus-maze, open field, aggressiveness) performed subsequently revealed only minor changes in motor performance (MIS vs. controls). The MIS habitat will not, on its own, produce major effects that could confound interpretation of data induced by microgravity exposure during spaceflight. Our results may be even more helpful in developing multidisciplinary protocols with adequate scenarios addressing molecular to systems levels using mice of various genetic phenotypes in many laboratories

Developmental learning impairments in a rodent model of nodular heterotopia

Developmental malformations of neocortex—including microgyria, ectopias, and periventricular nodular heterotopia (PNH)—have been associated with language learning impairments in humans. Studies also show that developmental language impairments are frequently associated with deficits in processing rapid acoustic stimuli, and rodent models have linked cortical developmental disruption (microgyria, ectopia) with rapid auditory processing deficits. We sought to extend this neurodevelopmental model to evaluate the effects of embryonic (E) day 15 exposure to the anti-mitotic teratogen methylazoxymethanol acetate (MAM) on auditory processing and maze learning in rats. Extensive cortical anomalies were confirmed in MAM-treated rats post mortem. These included evidence of laminar disruption, PNH, and hippocampal dysplasia. Juvenile auditory testing (P21–42) revealed comparable silent gap detection performance for MAM-treated and control subjects, indicating normal hearing and basic auditory temporal processing in MAM subjects. Juvenile testing on a more complex two-tone oddball task, however, revealed a significant impairment in MAM-treated as compared to control subjects. Post hoc analysis also revealed a significant effect of PNH severity for MAM subjects, with more severe disruption associated with greater processing impairments. In adulthood (P60–100), only MAM subjects with the most severe PNH condition showed deficits in oddball two-tone processing as compared to controls. However, when presented with a more complex and novel FM sweep detection task, all MAM subjects showed significant processing deficits as compared to controls. Moreover, post hoc analysis revealed a significant effect of PNH severity on FM sweep processing. Water Maze testing results also showed a significant impairment for spatial but not non-spatial learning in MAM rats as compared to controls. Results lend further support to the notions that: (1) generalized cortical developmental disruption (stemming from injury, genetic or teratogenic insults) leads to auditory processing deficits, which in turn have been suggested to play a causal role in language impairment; (2) severity of cortical disruption is related to the severity of processing impairments; (3) juvenile auditory processing deficits appear to ameliorate with maturation, but can still be elicited in adulthood using increasingly complex acoustic stimuli; and (4) malformations induced with MAM are also associated with generalized spatial learning deficits. These cumulative findings contribute to our understanding of the behavioral consequences of cortical developmental pathology, which may in turn elucidate mechanisms contributing to developmental language learning impairment in humans