Development of an Expert Knowledge-Based Genomic Variant Prioritisation Platform.

Considering the growing interest towards next generation sequencing (NGS) and data analysis, and the substantial challenges associated to fully exploiting these technologies and data without the proper experience, an expert knowledge-based user-friendly analytical tool was developed to allow non-bioinformatics experts to process NGS genomic data, automatically prioritise genomic variants and make their own annotations. This tool was developed using a user-centred methodology, where an iterative process was followed until a useful product was developed. This tool allows the users to set-up the pre-processing pipeline, filter the obtained data, annotate it using external and local databases (DBs) and help on deciding which variants are more relevant for each study, taking advantage of its customised expert-based scoring system. The end users involved in the project concluded that CRIBOMICS was easy to learn, use and interact with, reducing the analysis time and possible errors of variant prioritisation for genetic diagnosis.

Cortical fractal dimension predicts disability worsening in Multiple Sclerosis patients.

BACKGROUND: Fractal geometry measures the morphology of the brain and detects CNS damage. We aimed to assess the longitudinal changes on brain's fractal geometry and its predictive value for disease worsening in patients with Multiple Sclerosis (MS). METHODS: We prospectively analyzed 146 consecutive patients with relapsing-remitting MS with up to 5 years of clinical and brain MRI (3 T) assessments. The fractal dimension and lacunarity were calculated for brain regions using box-counting methods. Longitudinal changes were analyzed in mixed-effect models and the risk of disability accumulation were assessed using Cox Proportional Hazard regression analysis. RESULTS: There was a significant decrease in the fractal dimension and increases of lacunarity in different brain regions over the 5-year follow-up. Lower cortical fractal dimension increased the risk of disability accumulation for the Expanded Disability Status Scale [HR 0.9734, CI 0.8420-0.9125; Harrell C 0.59; Wald p 0.038], 9-hole peg test [HR 0.9734, CI 0.8420-0.9125; Harrell C 0.59; Wald p 0.0083], 2.5% low contrast vision [HR 0.4311, CI 0.2035-0.9133; Harrell C 0.58; Wald p 0.0403], symbol digit modality test [HR 2.215, CI 1.043-4.705; Harrell C 0.65; Wald p 0.0384] and MS Functional Composite-4 [HR 0.55, CI 0.317-0.955; Harrell C 0.59; Wald p 0.0029]. CONCLUSIONS: Fractal geometry analysis of brain MRI identified patients at risk of increasing their disability in the next five years.

Breast pectoral muscle segmentation in mammograms using a modified holistically-nested edge detection network.

This paper presents a method for automatic breast pectoral muscle segmentation in mediolateral oblique mammograms using a Convolutional Neural Network (CNN) inspired by the Holistically-nested Edge Detection (HED) network. Most of the existing methods in the literature are based on hand-crafted models such as straight-line, curve-based techniques or a combination of both. Unfortunately, such models are insufficient when dealing with complex shape variations of the pectoral muscle boundary and when the boundary is unclear due to overlapping breast tissue. To compensate for these issues, we propose a neural network framework that incorporates multi-scale and multi-level learning, capable of learning complex hierarchical features to resolve spatial ambiguity in estimating the pectoral muscle boundary. For this purpose, we modified the HED network architecture to specifically find 'contour-like' objects in mammograms. The proposed framework produced a probability map that can be used to estimate the initial pectoral muscle boundary. Subsequently, we process these maps by extracting morphological properties to find the actual pectoral muscle boundary. Finally, we developed two different post-processing steps to find the actual pectoral muscle boundary. Quantitative evaluation results show that the proposed method is comparable with alternative state-of-the-art methods producing on average values of 94.8 ±â€¯8.5% and 97.5 ±â€¯6.3% for the Jaccard and Dice similarity metrics, respectively, across four different databases.

Fully automatic detection and segmentation of abdominal aortic thrombus in post-operative CTA images using Deep Convolutional Neural Networks.

Computerized Tomography Angiography (CTA) based follow-up of Abdominal Aortic Aneurysms (AAA) treated with Endovascular Aneurysm Repair (EVAR) is essential to evaluate the progress of the patient and detect complications. In this context, accurate quantification of post-operative thrombus volume is required. However, a proper evaluation is hindered by the lack of automatic, robust and reproducible thrombus segmentation algorithms. We propose a new fully automatic approach based on Deep Convolutional Neural Networks (DCNN) for robust and reproducible thrombus region of interest detection and subsequent fine thrombus segmentation. The DetecNet detection network is adapted to perform region of interest extraction from a complete CTA and a new segmentation network architecture, based on Fully Convolutional Networks and a Holistically-Nested Edge Detection Network, is presented. These networks are trained, validated and tested in 13 post-operative CTA volumes of different patients using a 4-fold cross-validation approach to provide more robustness to the results. Our pipeline achieves a Dice score of more than 82% for post-operative thrombus segmentation and provides a mean relative volume difference between ground truth and automatic segmentation that lays within the experienced human observer variance without the need of human intervention in most common cases.

MR-guided thermotherapy of abdominal organs using a robust PCA-based motion descriptor.

Thermotherapies can now be guided in real-time using magnetic resonance imaging (MRI). This technique is rapidly gaining importance in interventional therapies for abdominal organs such as liver and kidney. An accurate online estimation and characterization of organ displacement is mandatory to prevent misregistration and correct for motion related thermometry artifacts. In addition, when the ablation is performed with an extracorporal heating device such as high intensity focused ultrasound (HIFU), the continuous estimation of the organ displacement is the basis for the dynamic adjustment of the focal point position to track the targeted pathological tissue. In this paper, we describe the use of an optimized principal component analysis (PCA)-based motion descriptor to characterize in real-time the complex organ deformation during the therapy. The PCA was used to detect, in a preparative learning step, spatio-temporal coherences in the motion of the targeted organ. During hyperthermia, incoherent motion patterns could be discarded, which enabled improvements in motion estimation robustness, the compensation of motion related errors in thermal maps, and the adjustment of the beam position. The suggested method was evaluated for a moving phantom, and tested in vivo in the kidney and the liver of 12 healthy volunteers under free breathing conditions. The ability to perform a MR-guided thermotherapy in vivo during HIFU intervention was finally demonstrated on a porcine kidney.

Real-time volumetric MRI thermometry of focused ultrasound ablation in vivo: a feasibility study in pig liver and kidney.

MR thermometry offers the possibility to precisely guide high-intensity focused ultrasound (HIFU) for the noninvasive treatment of kidney and liver tumours. The objectives of this study were to demonstrate therapy guidance by motion-compensated, rapid and volumetric MR temperature monitoring and to evaluate the feasibility of MR-guided HIFU ablation in these organs. Fourteen HIFU sonications were performed in the kidney and liver of five pigs under general anaesthesia using an MR-compatible Philips HIFU platform prototype. HIFU sonication power and duration were varied. Volumetric MR thermometry was performed continuously at 1.5 T using the proton resonance frequency shift method employing a multi-slice, single-shot, echo-planar imaging sequence with an update frequency of 2.5 Hz. Motion-related suceptibility artefacts were compensated for using multi-baseline reference images acquired prior to sonication. At the end of the experiment, the animals were sacrificed for macroscopic and microscopic examinations of the kidney, liver and skin. The standard deviation of the temperature measured prior to heating in the sonicated area was approximately 1 °C in kidney and liver, and 2.5 °C near the skin. The maximum temperature rise was 30 °C for a sonication of 1.2 MHz in the liver over 15 s at 300 W. The thermal dose reached the lethal threshold (240 CEM(43) ) in two of six cases in the kidney and four of eight cases in the liver, but remained below this value in skin regions in the beam path. These findings were in agreement with histological analysis. Volumetric thermometry allows real-time monitoring of the temperature at the target location in liver and kidney, as well as in surrounding tissues. Thermal ablation was more difficult to achieve in renal than in hepatic tissue even using higher acoustic energy, probably because of a more efficient heat evacuation in the kidney by perfusion.