Advances in machine learning applications for cardiovascular 4D flow MRI

Four-dimensional flow magnetic resonance imaging (MRI) has evolved as a non-invasive imaging technique to visualize and quantify blood flow in the heart and vessels. Hemodynamic parameters derived from 4D flow MRI, such as net flow and peak velocities, but also kinetic energy, turbulent kinetic energy, viscous energy loss, and wall shear stress have shown to be of diagnostic relevance for cardiovascular diseases. 4D flow MRI, however, has several limitations. Its long acquisition times and its limited spatio-temporal resolutions lead to inaccuracies in velocity measurements in small and low-flow vessels and near the vessel wall. Additionally, 4D flow MRI requires long post-processing times, since inaccuracies due to the measurement process need to be corrected for and parameter quantification requires 2D and 3D contour drawing. Several machine learning (ML) techniques have been proposed to overcome these limitations. Existing scan acceleration methods have been extended using ML for image reconstruction and ML based super-resolution methods have been used to assimilate high-resolution computational fluid dynamic simulations and 4D flow MRI, which leads to more realistic velocity results. ML efforts have also focused on the automation of other post-processing steps, by learning phase corrections and anti-aliasing. To automate contour drawing and 3D segmentation, networks such as the U-Net have been widely applied. This review summarizes the latest ML advances in 4D flow MRI with a focus on technical aspects and applications. It is divided into the current status of fast and accurate 4D flow MRI data generation, ML based post-processing tools for phase correction and vessel delineation and the statistical evaluation of blood flow

Effects of aging and dual tasking on step adjustments to perturbations in visually cued walking

Making step adjustments is an essential component of walking. However, the ability to make step adjustments may be compromised when the walker's attentional capacity is limited. This study compared the effects of aging and dual tasking on step adjustments in response to stepping-target perturbations during visually cued treadmill walking. Fifteen older adults (69.4 ± 5.0 years; mean ± SD) and fifteen young adults (25.4 ± 3.0 years) walked at a speed of 3 km/h on a treadmill. Both groups performed visually cued step adjustments in response to unpredictable shifts of projected stepping targets in forward (FW), backward (BW) or sideward (SW) directions, at different levels of task difficulty [which increased as the available response distance (ARD) decreased], and with and without dual tasking (auditory Stroop task). In both groups, step adjustments were smaller than required. For FW and BW shifts, older adults undershot more under dual-task conditions. For these shifts, ARD affected the age groups differentially. For SW shifts, larger errors were found for older adults, dual tasking and the most difficult ARD. Stroop task performance did not differ between groups in all conditions. Older adults have more difficulty than young adults to make corrective step adjustments while walking, especially under dual-tasking conditions. Furthermore, they seemed to prioritize the cognitive task over the step adjustment task, a strategy that may pose aging populations at a greater fall risk. For comparable task difficulty, the older adults performed considerably worse than the young adults, indicating a decreased ability to adjust steps under time pressure

Mitral valve regurgitation assessed by intraventricular CMR 4D-flow: a systematic review on the technological aspects and potential clinical applications.

Cardiac magnetic resonance (CMR) four-dimensional (4D) flow is a novel method for flow quantification potentially helpful in management of mitral valve regurgitation (MVR). In this systematic review, we aimed to depict the clinical role of intraventricular 4D-flow in MVR. The reproducibility, technical aspects, and comparison against conventional techniques were evaluated. Published studies on SCOPUS, MEDLINE, and EMBASE were included using search terms on 4D-flow CMR in MVR. Out of 420 screened articles, 18 studies fulfilled our inclusion criteria. All studies (n = 18, 100%) assessed MVR using 4D-flow intraventricular annular inflow (4D-flowAIM) method, which calculates the regurgitation by subtracting the aortic forward flow from the mitral forward flow. Thereof, 4D-flow jet quantification (4D-flowjet) was assessed in 5 (28%), standard 2D phase-contrast (2D-PC) flow imaging in 8 (44%) and the volumetric method (the deviation of left ventricle stroke volume and right ventricular stroke volume) in 2 (11%) studies. Inter-method correlations among the 4 MVR quantification methods were heterogeneous across studies, ranging from moderate to excellent correlations. Two studies compared 4D-flowAIM to echocardiography with moderate correlation. In 12 (63%) studies the reproducibility of 4D-flow techniques in quantifying MVR was studied. Thereof, 9 (75%) studies investigated the reproducibility of the 4D-flowAIM method and the majority (n = 7, 78%) reported good to excellent intra- and inter-reader reproducibility. Intraventricular 4D-flowAIM provides high reproducibility with heterogeneous correlations to conventional quantification methods. Due to the absence of a gold standard and unknown accuracies, future longitudinal outcome studies are needed to assess the clinical value of 4D-flow in the clinical setting of MVR

Does having a twin-brother make for a bigger brain?

Objective: Brain volume of boys is larger than that of girls by ∼10%. Prenatal exposure to testosterone has been suggested in the masculinization of the brain. For example, in litter-bearing mammals intrauterine position increases prenatal testosterone exposure through adjacent male fetuses, resulting in masculinization of brain morphology. Design: The influence of intrauterine presence of a male co-twin on masculinization of human brain volume was studied in 9-year old twins. Methods: Magnetic resonance imaging brain scans, current testosterone, and estradiol levels were acquired from four groups of dizygotic (DZ) twins: boys from same-sex twin-pairs (SSM), boys from opposite-sex twin-pairs (OSM), girls from opposite-sex twin-pairs (OSF), and girls from same-sex twin-pairs (SSF; n=119 individuals). Data on total brain, cerebellum, gray and white matter volumes were examined. Results: Irrespective of their own sex, children with a male co-twin as compared to children with a female co-twin had larger total brain (+2.5%) and cerebellum (+5.5%) volumes. SSM, purportedly exposed to the highest prenatal testosterone levels, were found to have the largest volumes, followed by OSM, OSF and SSF children. Birth weight partly explained the effect on brain volumes. Current testosterone and estradiol levels did not account for the volumetric brain differences. However, the effects observed in children did not replicate in adult twins. Conclusions: Our study indicates that sharing the uterus with a DZ twin brother increases total brain volume in 9-year olds. The effect may be transient and limited to a critical period in childhood. © 2009 European Society of Endocrinology

A novel and simple test of gait adaptability predicts gold standard measures of functional mobility in stroke surviveors

Background Although there is evidence that stroke survivors have reduced gait adaptability, the underlying mechanisms and the relationship to functional recovery are largely unknown. We explored the relationships between walking adaptability and clinical measures of balance, motor recovery and functional ability in stroke survivors. Methods Stroke survivors (n = 42) stepped to targets, on a 6 m walkway, placed to elicit step lengthening, shortening and narrowing on paretic and non-paretic sides. The number of targets missed during six walks and target stepping speed was recorded. Fugl–Meyer (FM), Berg Balance Scale (BBS), self-selected walking speed (SWWS) and single support (SS) and step length (SL) symmetry (using GaitRite when not walking to targets) were also assessed. Stepwise multiple-linear regression was used to model the relationships between: total targets missed, number missed with paretic and non-paretic legs, target stepping speed, and each clinical measure. Results Regression revealed a significant model for each outcome variable that included only one independent variable. Targets missed by the paretic limb, was a significant predictor of FM (F(1,40) = 6.54, p = 0.014,). Speed of target stepping was a significant predictor of each of BBS (F(1,40) = 26.36, p < 0.0001), SSWS (F(1,40) = 37.00, p < 0.0001). No variables were significant predictors of SL or SS asymmetry. Discussion Speed of target stepping was significantly predictive of BBS and SSWS and paretic targets missed predicted FM, suggesting that fast target stepping requires good balance and accurate stepping demands good paretic leg function. The relationships between these parameters indicate gait adaptability is a clinically meaningful target for measurement and treatment of functionally adaptive walking ability in stroke survivors

Getting the phase consistent: The importance of phase description in balanced steady-state free precession MRI of multicompartment systems

Purpose: Determine the correct mathematical phase description for balanced steady-state free precession (bSSFP) signals in multicompartment systems. Theory and Methods: Based on published bSSFP signal models, two distinct phase descriptions can be formulated: one predicting the presence and the other predicting the absence of destructive interference effects in multicompartment systems. Numerical simulations of bSSFP signals of water and acetone were performed to evaluate the predictions of these two distinct phase descriptions. For experimental validation, bSSFP profiles were measured at 3T using phase-cycled bSSFP acquisitions performed in a phantom containing mixtures of water and acetone, which replicates a system with two signal components. Localized single voxel MRS was performed at 7T to determine the relative chemical-shift of the acetone-water mixtures. Results: Based on the choice of phase description, the simulated bSSFP profiles of water-acetone mixtures varied significantly, either displaying or lacking destructive interference effects, as predicted theoretically. In phantom experiments, destructive interference was consistently observed in the measured bSSFP profiles of water-acetone mixtures, an observation which excludes the phase description that predicts an absence of destructive interference. The connection between the choice of phase description and predicted observation enables an unambiguous experimental identification of the correct phase description for multicompartment bSSFP profiles, which is consistent with Bloch equations. Conclusion: The study emphasizes that consistent phase descriptions are crucial for accurately describing multi-compartment bSSFP signals, as incorrect phase descriptions result in erroneous predictions.Comment: Submitted to Magn. Reson. Me

Key Features Relevant to Select Antigens and TCR From the MHC-Mismatched Repertoire to Treat Cancer

Adoptive transfer of T cells transgenic for tumor-reactive T-cell receptors (TCR) is an attractive immunotherapeutic approach. However, clinical translation is so far limited due to challenges in the identification of suitable target antigens as well as TCRs that are concurrent safe and efficient. Definition of key characteristics relevant for effective and specific tumor rejection is essential to improve current TCR-based adoptive T-cell immunotherapies. We here characterized in-depth two TCRs derived from the human leukocyte antigen (HLA)-mismatched allogeneic repertoire targeting two different myeloperoxidase (MPO)-derived peptides presented by the same HLA-restriction element side by side comprising state of the art biochemical and cellular in vitro, in vivo, and in silico experiments. In vitro experiments reveal comparable functional avidities, off-rates, and cytotoxic activities for both TCRs. However, we observed differences especially with respect to cytokine secretion and cross-reactivity as well as in vivo activity. Biochemical and in silico analyses demonstrate different binding qualities of MPO-peptides to the HLA-complex determining TCR qualities. We conclude from our biochemical and in silico analyses of peptide-HLA-binding that rigid and high-affinity binding of peptides is one of the most important factors for isolation of TCRs with high specificity and tumor rejection capacity from the MHC-mismatched repertoire. Based on our results, we developed a workflow for selection of such TCRs with high potency and safety profile suitable for clinical translation

Genetic Covariance Structure of Reading, Intelligence and Memory in Children

This study investigates the genetic relationship among reading performance, IQ, verbal and visuospatial working memory (WM) and short-term memory (STM) in a sample of 112, 9-year-old twin pairs and their older siblings. The relationship between reading performance and the other traits was explained by a common genetic factor for reading performance, IQ, WM and STM and a genetic factor that only influenced reading performance and verbal memory. Genetic variation explained 83% of the variation in reading performance; most of this genetic variance was explained by variation in IQ and memory performance. We hypothesize, based on these results, that children with reading problems possibly can be divided into three groups: (1) children low in IQ and with reading problems; (2) children with average IQ but a STM deficit and with reading problems; (3) children with low IQ and STM deficits; this group may experience more reading problems than the other two