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

Fast left ventricle tracking in CMR images using localized anatomical affine optical flow

"Progress in Biomedical Optics and Imaging, vol. 16, nr. 41"In daily cardiology practice, assessment of left ventricular (LV) global function using non-invasive imaging remains central for the diagnosis and follow-up of patients with cardiovascular diseases. Despite the different methodologies currently accessible for LV segmentation in cardiac magnetic resonance (CMR) images, a fast and complete LV delineation is still limitedly available for routine use. In this study, a localized anatomically constrained affine optical flow method is proposed for fast and automatic LV tracking throughout the full cardiac cycle in short-axis CMR images. Starting from an automatically delineated LV in the end-diastolic frame, the endocardial and epicardial boundaries are propagated by estimating the motion between adjacent cardiac phases using optical flow. In order to reduce the computational burden, the motion is only estimated in an anatomical region of interest around the tracked boundaries and subsequently integrated into a local affine motion model. Such localized estimation enables to capture complex motion patterns, while still being spatially consistent. The method was validated on 45 CMR datasets taken from the 2009 MICCAI LV segmentation challenge. The proposed approach proved to be robust and efficient, with an average distance error of 2.1 mm and a correlation with reference ejection fraction of 0.98 (1.9 ± 4.5%). Moreover, it showed to be fast, taking 5 seconds for the tracking of a full 4D dataset (30 ms per image). Overall, a novel fast, robust and accurate LV tracking methodology was proposed, enabling accurate assessment of relevant global function cardiac indices, such as volumes and ejection fraction.The authors acknowledge funding support from FCT - Fundação para a Ciência e Tecnologia, Portugal, in the scope of the PhD grant SFRH/BD/93443/2013 and the project EXPL/BBB-BMD/2473/2013. D. Barbosa would also like to acknowledge the kind support of the Fundação Luso-Americana para o Desenvolvimento (FLAD), which has funded the travel costs for participation at SPIE Medical Imaging 2015.info:eu-repo/semantics/publishedVersio

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

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

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

HIV-1 matrix protein p17 misfolding forms toxic amyloidogenic assemblies that induce neurocognitive disorders

© 2017 The Author(s). Human immunodeficiency virus type-1 (HIV-1)-Associated neurocognitive disorder (HAND) remains an important neurological manifestation that adversely affects a patient's quality of life. HIV-1 matrix protein p17 (p17) has been detected in autoptic brain tissue of HAND individuals who presented early with severe AIDS encephalopathy. We hypothesised that the ability of p17 to misfold may result in the generation of toxic assemblies in the brain and may be relevant for HAND pathogenesis. A multidisciplinary integrated approach has been applied to determine the ability of p17 to form soluble amyloidogenic assemblies in vitro. To provide new information into the potential pathogenic role of soluble p17 species in HAND, their toxicological capability was evaluated in vivo. In C. elegans, capable of recognising toxic assemblies of amyloidogenic proteins, p17 induces a specific toxic effect which can be counteracted by tetracyclines, drugs able to hinder the formation of large oligomers and consequently amyloid fibrils. The intrahippocampal injection of p17 in mice reduces their cognitive function and induces behavioral deficiencies. These findings offer a new way of thinking about the possible cause of neurodegeneration in HIV-1-seropositive patients, which engages the ability of p17 to form soluble toxic assemblies