Revealing Hidden Potentials of the q-Space Signal in Breast Cancer

Mammography screening for early detection of breast lesions currently suffers from high amounts of false positive findings, which result in unnecessary invasive biopsies. Diffusion-weighted MR images (DWI) can help to reduce many of these false-positive findings prior to biopsy. Current approaches estimate tissue properties by means of quantitative parameters taken from generative, biophysical models fit to the q-space encoded signal under certain assumptions regarding noise and spatial homogeneity. This process is prone to fitting instability and partial information loss due to model simplicity. We reveal unexplored potentials of the signal by integrating all data processing components into a convolutional neural network (CNN) architecture that is designed to propagate clinical target information down to the raw input images. This approach enables simultaneous and target-specific optimization of image normalization, signal exploitation, global representation learning and classification. Using a multicentric data set of 222 patients, we demonstrate that our approach significantly improves clinical decision making with respect to the current state of the art.Comment: Accepted conference paper at MICCAI 201

Magnetic Resonance Imaging-Guided Transurethral Ultrasound Ablation of Prostate Cancer

Purpose: Magnetic resonance imaging-guided transurethral ultrasound ablation uses directional thermal ultrasound under magnetic resonance imaging thermometry feedback control for prostatic ablation. We report 12-month outcomes from a prospective multicenter trial (TACT). Materials and methods: A total of 115 men with favorable to intermediate risk prostate cancer across 13 centers were treated with whole gland ablation sparing the urethra and apical sphincter. The co-primary 12-month endpoints were safety and efficacy. Results: In all, 72 (63%) had grade group 2 and 77 (67%) had NCCN® intermediate risk disease. Median treatment delivery time was 51 minutes with 98% (IQR 95-99) thermal coverage of target volume and spatial ablation precision of ±1.4 mm on magnetic resonance imaging thermometry. Grade 3 adverse events occurred in 9 (8%) men. The primary endpoint (U.S. Food and Drug Administration mandated) of prostate specific antigen reduction ≥75% was achieved in 110 of 115 (96%) with median prostate specific antigen reduction of 95% and nadir of 0.34 ng/ml. Median prostate volume decreased from 37 to 3 cc. Among 68 men with pretreatment grade group 2 disease, 52 (79%) were free of grade group 2 disease on 12-month biopsy. Of 111 men with 12-month biopsy data, 72 (65%) had no evidence of cancer. Erections (International Index of Erectile Function question 2 score 2 or greater) were maintained/regained in 69 of 92 (75%). Multivariate predictors of persistent grade group 2 at 12 months included intraprostatic calcifications at screening, suboptimal magnetic resonance imaging thermal coverage of target volume and a PI-RADS™ 3 or greater lesion at 12-month magnetic resonance imaging (p <0.05). Conclusions: The TACT study of magnetic resonance imaging-guided transurethral ultrasound whole gland ablation in men with localized prostate cancer demonstrated effective tissue ablation and prostate specific antigen reduction with low rates of toxicity and residual disease

Multicentre evaluation of targeted and systematic biopsies using magnetic resonance and ultrasound image-fusion guided transperineal prostate biopsy in patients with a previous negative biopsy.

OBJECTIVES: To evaluate the detection rates of targeted and systematic biopsies in magnetic resonance imaging (MRI) and ultrasound (US) image-fusion transperineal prostate biopsy for patients with previous benign transrectal biopsies in two high-volume centres. PATIENTS AND METHODS: A two centre prospective outcome study of 487 patients with previous benign biopsies that underwent transperineal MRI/US fusion-guided targeted and systematic saturation biopsy from 2012 to 2015. Multiparametric MRI (mpMRI) was reported according to Prostate Imaging Reporting and Data System (PI-RADS) Version 1. Detection of Gleason score 7-10 prostate cancer on biopsy was the primary outcome. Positive (PPV) and negative (NPV) predictive values including 95% confidence intervals (95% CIs) were calculated. Detection rates of targeted and systematic biopsies were compared using McNemar's test. RESULTS: The median (interquartile range) PSA level was 9.0 (6.7-13.4) ng/mL. PI-RADS 3-5 mpMRI lesions were reported in 343 (70%) patients and Gleason score 7-10 prostate cancer was detected in 149 (31%). The PPV (95% CI) for detecting Gleason score 7-10 prostate cancer was 0.20 (±0.07) for PI-RADS 3, 0.32 (±0.09) for PI-RADS 4, and 0.70 (±0.08) for PI-RADS 5. The NPV (95% CI) of PI-RADS 1-2 was 0.92 (±0.04) for Gleason score 7-10 and 0.99 (±0.02) for Gleason score ≥4 + 3 cancer. Systematic biopsies alone found 125/138 (91%) Gleason score 7-10 cancers. In patients with suspicious lesions (PI-RADS 4-5) on mpMRI, systematic biopsies would not have detected 12/113 significant prostate cancers (11%), while targeted biopsies alone would have failed to diagnose 10/113 (9%). In equivocal lesions (PI-RADS 3), targeted biopsy alone would not have diagnosed 14/25 (56%) of Gleason score 7-10 cancers, whereas systematic biopsies alone would have missed 1/25 (4%). Combination with PSA density improved the area under the curve of PI-RADS from 0.822 to 0.846. CONCLUSION: In patients with high probability mpMRI lesions, the highest detection rates of Gleason score 7-10 cancer still required combined targeted and systematic MRI/US image-fusion; however, systematic biopsy alone may be sufficient in patients with equivocal lesions. Repeated prostate biopsies may not be needed at all for patients with a low PSA density and a negative mpMRI read by experienced radiologists.N. Hansen has received a research grant from RWTH Aachen University Hospital (Aachen, Germany). T. Barrett acknowledges support from Cancer Research UK, National Institute of Health Research Cambridge Biomedical Research Centre, Cancer Research UK and the Engineering and Physical Sciences Research Council Imaging Centre in Cambridge and Manchester and the Cambridge Experimental Cancer Medicine Centre. A. Warren acknowledges support from the National Institute for Health Research Cambridge Biomedical Research Centre UK. C. Kastner acknowledges that he has received speaker or mentorship fees from Siemens Healthcare and MedCom GmbH. The Department of Urology, Addenbrooke's Hospital, Cambridge, UK, also received sponsorship of various industry for organising Prostate MRI workshops. B. Hadaschik acknowledges support from the German Research Foundation

Use of satellite observations for operational oceanography: recent achievements and future prospects

The paper gives an overview of the development of satellite oceanography over the past five years focusing on the most relevant issues for operational oceanography. Satellites provide key essential variables to constrain ocean models and/or serve downstream applications. New and improved satellite data sets have been developed and have directly improved the quality of operational products. The status of the satellite constellation for the last five years was, however, not optimal. Review of future missions shows clear progress and new research and development missions with a potentially large impact for operational oceanography should be demonstrated. Improvement of data assimilation techniques and developing synergetic use of high resolution satellite observations are important future priorities

ACBD5 and VAPB mediate membrane associations between peroxisomes and the ER

This is the final version of the article. Available from the publisher via the DOI in this record.Peroxisomes (POs) and the endoplasmic reticulum (ER) cooperate in cellular lipid metabolism and form tight structural associations, which were first observed in ultrastructural studies decades ago. PO–ER associations have been suggested to impact on a diverse number of physiological processes, including lipid metabolism, phospholipid exchange, metabolite transport, signaling, and PO biogenesis. Despite their fundamental importance to cell metabolism, the mechanisms by which regions of the ER become tethered to POs are unknown, in particular in mammalian cells. Here, we identify the PO membrane protein acyl-coenzyme A–binding domain protein 5 (ACBD5) as a binding partner for the resident ER protein vesicle-associated membrane protein-associated protein B (VAPB). We show that ACBD5–VAPB interaction regulates PO–ER associations. Moreover, we demonstrate that loss of PO–ER association perturbs PO membrane expansion and increases PO movement. Our findings reveal the first molecular mechanism for establishing PO–ER associations in mammalian cells and report a new function for ACBD5 in PO–ER tethering.This work was supported by grants from the Biotechnology and Biological Sciences Research Council (BB/K006231/1 and BB/ N01541X/1 to M. Schrader). J. Metz and M. Schrader are supported by a Wellcome Trust Institutional Strategic Support Award (WT097835MF and WT105618MA) and L.F. Godinho by a fellowship from Fundação para a Ciência e a Tecnologia, Portugal (SFRH/ BPD/90084/2012). M. Schrader and A.S. Azadi are supported by Marie Curie Initial Training Network action PerFuMe (316723). M. Islinger is supported by MEAMEDMA Anschubförderung, Medical Faculty Mannheim, University of Heidelberg

Reevaluation of the role of Pex1 and dynamin-related proteins in peroxisome membrane biogenesis

A recent model for peroxisome biogenesis postulates that peroxisomes form de novo continuously in wild-type cells by heterotypic fusion of endoplasmic reticulum–derived vesicles containing distinct sets of peroxisomal membrane proteins. This model proposes a role in vesicle fusion for the Pex1/Pex6 complex, which has an established role in matrix protein import. The growth and division model proposes that peroxisomes derive from existing peroxisomes. We tested these models by reexamining the role of Pex1/Pex6 and dynamin-related proteins in peroxisome biogenesis. We found that induced depletion of Pex1 blocks the import of matrix proteins but does not affect membrane protein delivery to peroxisomes; markers for the previously reported distinct vesicles colocalize in pex1 and pex6 cells; peroxisomes undergo continued growth if ission is blocked. Our data are compatible with the established primary role of the Pex1/Pex6 complex in matrix protein import and show that peroxisomes in Saccharomyces cerevisiae multiply mainly by growth and division

A Comparative Evaluation of Voxel-based Spatial Mapping in Diffusion Tensor Imaging

This paper presents a comparative evaluation of methods for automated voxel-based spatial mapping in diffusion tensor imaging studies. Such methods are an essential step in computational pipelines and provide anatomically comparable measurements across a population in atlas-based studies. To better understand their strengths and weaknesses, we tested a total of eight methods for voxel-based spatial mapping in two types of diffusion tensor templates. The methods were evaluated with respect to scan-rescan reliability and an application to normal aging. The methods included voxel-based analysis with and without smoothing, two types of region-based analysis, and combinations thereof with skeletonization. The templates included a study-specific template created with DTI-TK and the IIT template serving as a standard template. To control for other factors in the pipeline, the experiments used a common dataset, acquired at 1.5T with a single shell high angular resolution diffusion MR imaging protocol, and tensor-based spatial normalization with DTI-TK. Scan-rescan reliability was assessed using the coefficient of variation (CV) and intraclass correlation (ICC) in eight subjects with three scans each. Sensitivity to normal aging was assessed in a population of 80 subjects aged 25 to 65 years old, and methods were compared with respect to the anatomical agreement of significant findings and the R(2) of the associated models of fractional anisotropy. The results show that reliability depended greatly on the method used for spatial mapping. The largest differences in reliability were found when adding smoothing and comparing voxel-based and region-based analyses. Skeletonization and template type were found to have either a small or negligible effect on reliability. The aging results showed agreement among the methods in nine brain areas, with some methods showing more sensitivity than others. Skeletonization and smoothing were not major factors affecting sensitivity to aging, but the standard template showed higher R(2) in several conditions. A structural comparison of the templates showed that large deformations between them may be related to observed differences in patterns of significant voxels. Most areas showed significantly higher R(2) with voxel-based analysis, particularly when clusters were smaller than the available regions-of-interest. Looking forward, these results can potentially help to interpret results from existing white matter imaging studies, as well as provide a resource to help in planning future studies to maximize reliability and sensitivity with regard to the scientific goals at hand