Lesion-conditioning of synthetic MRI-derived subtraction-MIPs of the breast using a latent diffusion model.

The purpose of this feasibility study is to investigate if latent diffusion models (LDMs) are capable to generate contrast enhanced (CE) MRI-derived subtraction maximum intensity projections (MIPs) of the breast, which are conditioned by lesions. We trained an LDM with n = 2832 CE-MIPs of breast MRI examinations of n = 1966 patients (median age: 50 years) acquired between the years 2015 and 2020. The LDM was subsequently conditioned with n = 756 segmented lesions from n = 407 examinations, indicating their location and BI-RADS scores. By applying the LDM, synthetic images were generated from the segmentations of an independent validation dataset. Lesions, anatomical correctness, and realistic impression of synthetic and real MIP images were further assessed in a multi-rater study with five independent raters, each evaluating n = 204 MIPs (50% real/50% synthetic images). The detection of synthetic MIPs by the raters was akin to random guessing with an AUC of 0.58. Interrater reliability of the lesion assessment was high both for real (Kendall's W = 0.77) and synthetic images (W = 0.85). A higher AUC was observed for the detection of suspicious lesions (BI-RADS ≥ 4) in synthetic MIPs (0.88 vs. 0.77; p = 0.051). Our results show that LDMs can generate lesion-conditioned MRI-derived CE subtraction MIPs of the breast, however, they also indicate that the LDM tended to generate rather typical or 'textbook representations' of lesions.

Smart forecasting of artifacts in contrast-enhanced breast MRI before contrast agent administration.

OBJECTIVES: To evaluate whether artifacts on contrast-enhanced (CE) breast MRI maximum intensity projections (MIPs) might already be forecast before gadolinium-based contrast agent (GBCA) administration during an ongoing examination by analyzing the unenhanced T1-weighted images acquired before the GBCA injection. MATERIALS AND METHODS: This IRB-approved retrospective analysis consisted of n = 2884 breast CE MRI examinations after intravenous administration of GBCA, acquired with n = 4 different MRI devices at different field strengths (1.5 T/3 T) during clinical routine. CE-derived subtraction MIPs were used to conduct a multi-class multi-reader evaluation of the presence and severity of artifacts with three independent readers. An ensemble classifier (EC) of five DenseNet models was used to predict artifacts for the post-contrast subtraction MIPs, giving as the input source only the pre-contrast T1-weighted sequence. Thus, the acquisition directly preceded the GBCA injection. The area under ROC (AuROC) and diagnostics accuracy scores were used to assess the performance of the neural network in an independent holdout test set (n = 285). RESULTS: After majority voting, potentially significant artifacts were detected in 53.6% (n = 1521) of all breast MRI examinations (age 49.6 ± 12.6 years). In the holdout test set (mean age 49.7 ± 11.8 years), at a specificity level of 89%, the EC could forecast around one-third of artifacts (sensitivity 31%) before GBCA administration, with an AuROC = 0.66. CONCLUSION: This study demonstrates the capability of a neural network to forecast the occurrence of artifacts on CE subtraction data before the GBCA administration. If confirmed in larger studies, this might enable a workflow-blended approach to prevent breast MRI artifacts by implementing in-scan personalized predictive algorithms. CLINICAL RELEVANCE STATEMENT: Some artifacts in contrast-enhanced breast MRI maximum intensity projections might be predictable before gadolinium-based contrast agent injection using a neural network. KEY POINTS: • Potentially significant artifacts can be observed in a relevant proportion of breast MRI subtraction sequences after gadolinium-based contrast agent administration (GBCA). • Forecasting the occurrence of such artifacts in subtraction maximum intensity projections before GBCA administration for individual patients was feasible at 89% specificity, which allowed correctly predicting one in three future artifacts. • Further research is necessary to investigate the clinical value of such smart personalized imaging approaches.

Elucidating the control and development of skin patterning in cuttlefish.

Few animals provide a readout that is as objective of their perceptual state as camouflaging cephalopods. Their skin display system includes an extensive array of pigment cells (chromatophores), each expandable by radial muscles controlled by motor neurons. If one could track the individual expansion states of the chromatophores, one would obtain a quantitative description-and potentially even a neural description by proxy-of the perceptual state of the animal in real time. Here we present the use of computational and analytical methods to achieve this in behaving animals, quantifying the states of tens of thousands of chromatophores at sixty frames per second, at single-cell resolution, and over weeks. We infer a statistical hierarchy of motor control, reveal an underlying low-dimensional structure to pattern dynamics and uncover rules that govern the development of skin patterns. This approach provides an objective description of complex perceptual behaviour, and a powerful means to uncover the organizational principles that underlie the function, dynamics and morphogenesis of neural systems.

Glyoxal as an alternative fixative to formaldehyde in immunostaining and super-resolution microscopy.

Paraformaldehyde (PFA) is the most commonly used fixative for immunostaining of cells, but has been associated with various problems, ranging from loss of antigenicity to changes in morphology during fixation. We show here that the small dialdehyde glyoxal can successfully replace PFA Despite being less toxic than PFA, and, as most aldehydes, likely usable as a fixative, glyoxal has not yet been systematically tried in modern fluorescence microscopy. Here, we tested and optimized glyoxal fixation and surprisingly found it to be more efficient than PFA-based protocols. Glyoxal acted faster than PFA, cross-linked proteins more effectively, and improved the preservation of cellular morphology. We validated glyoxal fixation in multiple laboratories against different PFA-based protocols and confirmed that it enabled better immunostainings for a majority of the targets. Our data therefore support that glyoxal can be a valuable alternative to PFA for immunostaining.

Cephalopod biology and care, a COST FA1301 (CephsInAction) training school: anaesthesia and scientific procedures.

Cephalopods are the sole invertebrates included in the list of regulated species following the Directive 2010/63/EU. According to the Directive, achieving competence through adequate training is a requisite for people having a role in the different functions (article 23) as such carrying out procedures on animals, designing procedures and projects, taking care of animals, killing animals. Cephalopod Biology and Care Training Program is specifically designed to comply with the requirements of the "working document on the development of a common education and training framework to fulfil the requirements under the Directive 2010/63/EU". The training event occurred at the ICM-CSIC in Barcelona (Spain) where people coming from Europe, America and Asia were instructed on how to cope with regulations for the use of cephalopod molluscs for scientific purposes. The training encompasses discussion on the guidelines for the use and care of animals and their welfare with particular reference to procedures that may be of interest for neuroscience. Intensive discussion has been carried out during the training sessions with focus on behavioural studies and paradigms, welfare assessment, levels of severity of scientific procedures, animal care, handling, transport, individual identification and marking, substance administration, anaesthesia, analgesia and humane killing.