A Cylindrical, Inner Volume Selecting 2D-T2-Prep Improves GRAPPA-Accelerated Image Quality in MRA of the Right Coronary Artery.

Two-dimensional (2D) spatially selective radiofrequency (RF) pulses may be used to excite restricted volumes. By incorporating a "pencil beam" 2D pulse into a T2-Prep, one may create a "2D-T2-Prep" that combines T2-weighting with an intrinsic outer volume suppression. This may particularly benefit parallel imaging techniques, where artefacts typically originate from residual foldover signal. By suppressing foldover signal with a 2D-T2-Prep, image quality may therefore improve. We present numerical simulations, phantom and in vivo validations to address this hypothesis. A 2D-T2-Prep and a conventional T2-Prep were used with GRAPPA-accelerated MRI (R = 1.6). The techniques were first compared in numerical phantoms, where per pixel maps of SNR (SNRmulti), noise, and g-factor were predicted for idealized sequences. Physical phantoms, with compartments doped to mimic blood, myocardium, fat, and coronary vasculature, were scanned with both T2-Preparation techniques to determine the actual SNRmulti and vessel sharpness. For in vivo experiments, the right coronary artery (RCA) was imaged in 10 healthy adults, using accelerations of R = 1,3, and 6, and vessel sharpness was measured for each. In both simulations and phantom experiments, the 2D-T2-Prep improved SNR relative to the conventional T2-Prep, by an amount that depended on both the acceleration factor and the degree of outer volume suppression. For in vivo images of the RCA, vessel sharpness improved most at higher acceleration factors, demonstrating that the 2D-T2-Prep especially benefits accelerated coronary MRA. Suppressing outer volume signal with a 2D-T2-Prep improves image quality particularly well in GRAPPA-accelerated acquisitions in simulations, phantoms, and volunteers, demonstrating that it should be considered when performing accelerated coronary MRA

A characterization of cardiac-induced noise in R2* maps of the brain.

Cardiac pulsation increases the noise level in brain maps of the transverse relaxation rate R <sub>2</sub> *. Cardiac-induced noise is challenging to mitigate during the acquisition of R <sub>2</sub> * mapping data because its characteristics are unknown. In this work, we aim to characterize cardiac-induced noise in brain maps of the MRI parameter R <sub>2</sub> *. We designed a sampling strategy to acquire multi-echo 3D data in 12 intervals of the cardiac cycle, monitored with a fingertip pulse-oximeter. We measured the amplitude of cardiac-induced noise in this data and assessed the effect of cardiac pulsation on R <sub>2</sub> * maps computed across echoes. The area of k-space that contains most of the cardiac-induced noise in R <sub>2</sub> * maps was then identified. Based on these characteristics, we introduced a tentative sampling strategy that aims to mitigate cardiac-induced noise in R <sub>2</sub> * maps of the brain. In inferior brain regions, cardiac pulsation accounts for R <sub>2</sub> * variations of up to 3 s <sup>-1</sup> across the cardiac cycle (i.e., ∼35% of the overall variability). Cardiac-induced fluctuations occur throughout the cardiac cycle, with a reduced intensity during the first quarter of the cycle. A total of 50% to 60% of the overall cardiac-induced noise is localized near the k-space center (k < 0.074 mm <sup>-1</sup> ). The tentative cardiac noise mitigation strategy reduced the variability of R <sub>2</sub> * maps across repetitions by 11% in the brainstem and 6% across the whole brain. We provide a characterization of cardiac-induced noise in brain R <sub>2</sub> * maps that can be used as a basis for the design of mitigation strategies during data acquisition

The use of microscopy and three-dimensional visualization to evaluate the structure of microbial biofilms cultivated in the Calgary Biofilm Device

Microbes frequently live within multicellular, solid surface-attached assemblages termed biofilms. These microbial communities have architectural features that contribute to population heterogeneity and consequently to emergent cell functions. Therefore, three-dimensional (3D) features of biofilm structure are important for understanding the physiology and ecology of these microbial systems. This paper details several protocols for scanning electron microscopy and confocal laser scanning microscopy (CLSM) of biofilms grown on polystyrene pegs in the Calgary Biofilm Device (CBD). Furthermore, a procedure is described for image processing of CLSM data stacks using amira(™), a virtual reality tool, to create surface and/or volume rendered 3D visualizations of biofilm microorganisms. The combination of microscopy with microbial cultivation in the CBD – an apparatus that was designed for high-throughput susceptibility testing – allows for structure-function analysis of biofilms under multivariate growth and exposure conditions

Complement blockade with eculizumab to treat acute symptomatic humoral rejection after heart transplantation.

Antibody-mediated rejection (AMR) is a major barrier preventing successful discordant organ xenotransplantation, but it also occurs in allotransplantation due to anti-HLA antibodies. Symptomatic acute AMR is rare after heart allograft but carries a high risk of mortality, especially >1 year after transplant. As complement activation may play a major role in mediating tissue injury in acute AMR, drugs blocking the terminal complement cascade like eculizumab may be useful, particularly since "standards of care" like plasmapheresis are not based on strong evidence. Eculizumab was successfully used to treat early acute kidney AMR, a typical condition of "active AMR," but showed mitigated results in late AMR, where "chronic active" lesions are more prevalent. Here, we report the case of a heart recipient who presented with acute heart failure due to late acute AMR with eight de novo donor-specific anti-HLA antibodies (DSA), and who fully recovered allograft function and completely cleared DSA following plasmapheresis-free upfront eculizumab administration in addition to thymoglobulin, intravenous immunoglobulins (IVIG), and rituximab. Several clinical (acute onset, abrupt and severe loss of graft function), biological (sudden high-level production of DSA), and pathological features (microvascular injury, C4d deposits) of this cardiac recipient are shared with early kidney AMR and may indicate a strong role of complement in the pathogenesis of acute graft injury that may respond to drugs like eculizumab. Terminal complement blockade should be further explored to treat acute AMR in recipients of heart allografts and possibly also in recipients of discordant xenografts in the future

Fetal cardiac cine magnetic resonance imaging in utero.

Fast magnetic resonance imaging (MRI) led to the emergence of 'cine MRI' techniques, which enable the visualization of the beating heart and the assessment of cardiac morphology and dynamics. However, established cine MRI methods are not suitable for fetal heart imaging in utero, where anatomical structures are considerably smaller and recording an electrocardiogram signal for synchronizing MRI data acquisition is difficult. Here we present a framework to overcome these challenges. We use methods for image acquisition and reconstruction that robustly produce images with sufficient spatial and temporal resolution to detect the heart contractions of the fetus, enabling a retrospective gating of the images and thus the generation of images of the beating heart. To underline the potential of our approach, we acquired in utero images in six pregnant patients and compared these with their echocardiograms. We found good agreement in terms of diameter and area measurements, and low inter- and intra- observer variability. These results establish MRI as a reliable modality for fetal cardiac imaging, with a substantial potential for prenatal evaluation of congenital heart defects

Pattern formation in auxin flux

The plant hormone auxin is fundamental for plant growth, and its spatial distribution in plant tissues is critical for plant morphogenesis. We consider a leading model of the polar auxin flux, and study in full detail the stability of the possible equilibrium configurations. We show that the critical states of the auxin transport process are composed of basic building blocks, which are isolated in a background of auxin depleted cells, and are not geometrically regular in general. The same model was considered recently through a continuous limit and a coupling to the von Karman equations, to model the interplay of biochemistry and mechanics during plant growth. Our conclusions might be of interest in this setting, since, for example, we establish the existence of Lyapunov functions for the auxin flux, proving in this way the convergence of pure transport processes toward the set of equilibrium points

Motion-resolved fat-fraction mapping with whole-heart free-running multiecho GRE and pilot tone.

To develop a free-running 3D radial whole-heart multiecho gradient echo (ME-GRE) framework for cardiac- and respiratory-motion-resolved fat fraction (FF) quantification. (N <sub>TE</sub> = 8) readouts optimized for water-fat separation and quantification were integrated within a continuous non-electrocardiogram-triggered free-breathing 3D radial GRE acquisition. Motion resolution was achieved with pilot tone (PT) navigation, and the extracted cardiac and respiratory signals were compared to those obtained with self-gating (SG). After extra-dimensional golden-angle radial sparse parallel-based image reconstruction, FF, R <sub>2</sub> *, and B <sub>0</sub> maps, as well as fat and water images were generated with a maximum-likelihood fitting algorithm. The framework was tested in a fat-water phantom and in 10 healthy volunteers at 1.5 T using N <sub>TE</sub> = 4 and N <sub>TE</sub> = 8 echoes. The separated images and maps were compared with a standard free-breathing electrocardiogram (ECG)-triggered acquisition. The method was validated in vivo, and physiological motion was resolved over all collected echoes. Across volunteers, PT provided respiratory and cardiac signals in agreement (r = 0.91 and r = 0.72) with SG of the first echo, and a higher correlation to the ECG (0.1% of missed triggers for PT vs. 5.9% for SG). The framework enabled pericardial fat imaging and quantification throughout the cardiac cycle, revealing a decrease in FF at end-systole by 11.4% ± 3.1% across volunteers (p < 0.0001). Motion-resolved end-diastolic 3D FF maps showed good correlation with ECG-triggered measurements (FF bias of -1.06%). A significant difference in free-running FF measured with N <sub>TE</sub> = 4 and N <sub>TE</sub> = 8 was found (p < 0.0001 in sub-cutaneous fat and p < 0.01 in pericardial fat). Free-running fat fraction mapping was validated at 1.5 T, enabling ME-GRE-based fat quantification with N <sub>TE</sub> = 8 echoes in 6:15 min

Red cell distribution width and mortality in acute heart failure patients with preserved and reduced ejection fraction.

Elevated red blood cell distribution width (RDW) is a valid predictor of outcome in acute heart failure (AHF). It is unknown whether elevated RDW remains predictive in AHF patients with either preserved left ventricular ejection fraction (LVEF) ≥50% or reduced LVEF (<50%). Prospective local registry including 402 consecutive hospitalized AHF patients without acute coronary syndrome or need of intensive care. The primary outcome was all-cause mortality (ACM) at 1 year after admission. Demographic and clinical data derive from admission, echocardiographic examinations (n = 269; 67%) from hospitalization. The Cox proportional hazard model including all patients (P < 0.001) was adjusted for age, gender, and RDW quartiles. Independent predictors of 1-year ACM were cardiogenic shock (HR 2.86; CI: 1.3-6.4), male sex (HR 1.9; CI: 1.2-2.9), high RDW quartile (HR 1.66; CI: 1.02-2.8), chronic HF (HR 1.61; CI: 1.05-2.5), valvular heart disease (HR 1.61; CI: 1.09-2.4), increased diastolic blood pressure (HR 1.02 per mmHg; CI: 1.01-1.03), increasing age (HR 1.04 by year; CI: 1.02-1.07), platelet count (HR 1.002 per G/l; CI: 1.0-1.004), systolic blood pressure (HR 0.99 per mmHg; CI: 0.98-0.99), and weight (HR 0.98 per kg; CI: 0.97-0.99). A total of 114 patients (28.4%) died within the first year; ACM of all patients increased with quartiles of rising RDW (χ(2) 18; P < 0.001). ACM was not different between RDW quartiles of patients with reduced LVEF (n = 153; χ(2) 6.6; P = 0.084). In AHF with LVEF ≥50% the probability of ACM increased with rising RDW (n = 116; χ(2) 9.9; P = 0.0195). High RDW is associated with increased ACM in AHF patients with preserved but not with reduced LVEF in this study population

Minority Quasispecies of Drug-Resistant HIV-1 That Lead to Early Therapy Failure in Treatment-Naive and -Adherent Patients

Background.Early virological failure of antiretroviral therapy associated with the selection of drug-resistant human immunodeficiency virus type 1 in treatment-naive patients is very critical, because virological failure significantly increases the risk of subsequent failures. Therefore, we evaluated the possible role of minority quasispecies of drug-resistant human immunodeficiency virus type 1, which are undetectable at baseline by population sequencing, with regard to early virological failure. Methods.We studied 4 patients who experienced early virological failure of a first-line regimen of lamivudine, tenofovir, and either efavirenz or nevirapine and 18 control patients undergoing similar treatment without virological failure. The key mutations K65R, K103N, Y181C, M184V, and M184I in the reverse transcriptase were quantified by allele-specific real-time polymerase chain reaction performed on plasma samples before and during early virological treatment failure. Results.Before treatment, none of the viruses showed any evidence of drug resistance in the standard genotype analysis. Minority quasispecies with either the M184V mutation or the M184I mutation were detected in 3 of 18 control patients. In contrast, all 4 patients whose treatment was failing had harbored drug-resistant viruses at low frequencies before treatment, with a frequency range of 0.07% 2.0%. A range of 1 4 mutations was detected in viruses from each patient. Most of the minority quasispecies were rapidly selected and represented the major virus population within weeks after the patients started antiretroviral therapy. All 4 patients showed good adherence to treatment. Nonnucleoside reverse-transcriptase inhibitor plasma concentrations were in normal ranges for all 4 patients at 2 separate assessment times. Conclusions.Minority quasispecies of drug-resistant viruses, detected at baseline, can rapidly outgrow and become the major virus population and subsequently lead to early therapy failure in treatment-naive patients who receive antiretroviral therapy regimens with a low genetic resistance barrie

Reduced-iodine-dose dual-energy coronary CT angiography: qualitative and quantitative comparison between virtual monochromatic and polychromatic CT images.

To quantitatively evaluate the impact of virtual monochromatic images (VMI) on reduced-iodine-dose dual-energy coronary computed tomography angiography (CCTA) in terms of coronary lumen segmentation in vitro, and secondly to assess the image quality in vivo, compared with conventional CT obtained with regular iodine dose. A phantom simulating regular and reduced iodine injection was used to determine the accuracy and precision of lumen area segmentation for various VMI energy levels. We retrospectively included 203 patients from December 2017 to August 2018 (mean age, 51.7 ± 16.8 years) who underwent CCTA using either standard (group A, n = 103) or reduced (group B, n = 100) iodine doses. Conventional images (group A) were qualitatively and quantitatively compared with 55-keV VMI (group B). We recorded the location of venous catheters. In vitro, VMI outperformed conventional CT, with a segmentation accuracy of 0.998 vs. 1.684 mm <sup>2</sup> , respectively (p < 0.001), and a precision of 0.982 vs. 1.229 mm <sup>2</sup> , respectively (p < 0.001), in simulated overweight adult subjects. In vivo, the rate of diagnostic CCTA in groups A and B was 88.4% (n = 91/103) vs. 89% (n = 89/100), respectively, and noninferiority of protocol B was inferred. Contrast-to-noise ratios (CNR) of lumen versus fat and muscle were higher in group B (p < 0.001) and comparable for lumen versus calcium (p = 0.423). Venous catheters were more often placed on the forearm or hand in group B (p < 0.001). In vitro, low-keV VMI improve vessel area segmentation. In vivo, low-keV VMI allows for a 40% iodine dose and injection rate reduction while maintaining diagnostic image quality and improves the CNR between lumen versus fat and muscle. • Dual-energy coronary CT angiography is becoming increasingly available and might help improve patient management. • Compared with regular-iodine-dose coronary CT angiography, reduced-iodine-dose dual-energy CT with low-keV monochromatic image reconstructions performed better in phantom-based vessel cross-sectional segmentation and proved to be noninferior in vivo. • Patients receiving reduced-iodine-dose dual-energy coronary CT angiography often had the venous catheter placed on the forearm or wrist without compromising image quality