Yet more evidence that non-aqueous myelin lipids can be directly imaged with ultrashort echo time (UTE) MRI on a clinical 3T scanner: a lyophilized red blood cell membrane lipid study.

Direct imaging of semi-solid lipids, such as myelin, is of great interest as a noninvasive biomarker of neurodegenerative diseases. Yet, the short T2 relaxation times of semi-solid lipid protons hamper direct detection through conventional magnetic resonance imaging (MRI) pulse sequences. In this study, we examined whether a three-dimensional ultrashort echo time (3D UTE) sequence can directly acquire signals from membrane lipids. Membrane lipids from red blood cells (RBC) were collected from commercially available blood as a general model of the myelin lipid bilayer and subjected to D2O exchange and freeze-drying for complete water removal. Sufficiently high MR signals were detected with the 3D UTE sequence, which showed an ultrashort T2* of ∼77-271 µs and a short T1 of ∼189 ms for semi-solid RBC membrane lipids. These measurements can guide designing UTE-based sequences for direct in vivo imaging of membrane lipids.

Whole knee joint mapping using a phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence.

PURPOSE: To develop a 3D phase modulated UTE adiabatic T1ρ (PM-UTE-AdiabT1ρ ) sequence for whole knee joint mapping on a clinical 3 T scanner. METHODS: This new sequence includes six major features: (1) a magnetization reset module, (2) a train of adiabatic full passage pulses for spin locking, (3) a phase modulation scheme (i.e., RF cycling pair), (4) a fat saturation module, (5) a variable flip angle scheme, and (6) a 3D UTE Cones sequence for data acquisition. A simple exponential fitting was used for T1ρ quantification. Phantom studies were performed to investigate PM-UTE-AdiabT1ρ 's sensitivity to compositional changes and reproducibility as well as its correlation with continuous wave-T1ρ measurement. The PM-UTE-AdiabT1ρ technique was then applied to five ex vivo and five in vivo normal knees to measure T1ρ values of femoral cartilage, meniscus, posterior cruciate ligament, anterior cruciate ligament, patellar tendon, and muscle. RESULTS: The phantom study demonstrated PM-UTE-AdiabT1ρ 's high sensitivity to compositional changes, its high reproducibility, and its strong linear correlation with continuous wave-T1ρ measurement. The ex vivo and in vivo knee studies demonstrated average T1ρ values of 105.6 ± 8.4 and 77.9 ± 3.9 ms for the femoral cartilage, 39.2 ± 5.1 and 30.1 ± 2.2 ms for the meniscus, 51.6 ± 5.3 and 29.2 ± 2.4 ms for the posterior cruciate ligament, 79.0 ± 9.3 and 52.0 ± 3.1 ms for the anterior cruciate ligament, 19.8 ± 4.5 and 17.0 ± 1.8 ms for the patellar tendon, and 91.1 ± 8.8 and 57.6 ± 2.8 ms for the muscle, respectively. CONCLUSION: The 3D PM-UTE-AdiabT1ρ sequence allows volumetric T1ρ assessment for both short and long T2 tissues in the knee joint on a clinical 3 T scanner.

Apparent Diffusion Coefficient Reproducibility Across 3 T Scanners in a Breast Diffusion Phantom.

BACKGROUND: To date, the accuracy and variability of diffusion-weighted MRI (DW-MRI) metrics have been reported in a limited number of scanner/protocol/coil combinations. PURPOSE: To evaluate the reproducibility of DW-MRI estimates across multiple scanners and DW-MRI protocols and to assess the effects of using an 8-channel vs. 16-channel breast coil in a breast phantom. STUDY TYPE: Prospective. PHANTOM: Breast phantom containing tubes of water and differing polyvinylpyrrolidone (PVP) concentrations with apparent diffusion coefficients (ADCs) matching breast tissue. FIELD STRENGTH/SEQUENCE: 3 T (three standard and one wide bore), three DW-MRI single-shot echo planar imaging protocols of varying acquired spatial resolution. ASSESSMENT: Accuracy of estimated ADCs was assessed using percent differences (PD) relative to nuclear magnetic resonance spectroscopy-derived reference values. Coefficients of variation (CV) were calculated to determine variation across scanners. CVs based on the median standard deviation (CVM ) were used to evaluate tube-specific dispersion using 8- or 16-channel coils at a single scanner. ADCs of PVP-containing tubes were additionally normalized by the median water tube ADC to account for temperature effects. STATISTICAL TESTS: Two-way repeated measures analysis of variance and post hoc tests were used to evaluate differences in ADC, CV, and CVM across scanners and protocols (α = 0.05). RESULTS: ADCs were within 11% (interquartile range [IQR] 7%) of reference values and significantly improved to 2% (IQR 7%) after normalization to an internal water reference. Normalization significantly reduced interscanner variability of ADC estimates from 7% to 4%. DW-MRI protocol did not affect ADC accuracy; however, the clinical and higher-resolution clinical protocols resulted in the greatest (9%) and least (6%) interscanner variability, respectively. The 8- and 16-channel receive coils yielded similar accuracy (PD: 12% vs. 16%) and precision (CVM : 2.7% vs. 2.9%). DATA CONCLUSION: Normalization by an internal reference improved interscanner ADC reproducibility. High-resolution protocols yielded comparably accurate and significantly less variable ADCs compared to a clinical standard protocol. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Genome-wide association studies reveal novel loci for resistance to groundnut rosette disease in the African core groundnut collection.

KEY MESSAGE: We identified markers associated with GRD resistance after screening an Africa-wide core collection across three seasons in Uganda Groundnut is cultivated in several African countries where it is a major source of food, feed and income. One of the major constraints to groundnut production in Africa is groundnut rosette disease (GRD), which is caused by a complex of three agents: groundnut rosette assistor luteovirus, groundnut rosette umbravirus and its satellite RNA. Despite several years of breeding for GRD resistance, the genetics of the disease is not fully understood. The objective of the current study was to use the African core collection to establish the level of genetic variation in their response to GRD, and to map genomic regions responsible for the observed resistance. The African groundnut core genotypes were screened across two GRD hotspot locations in Uganda (Nakabango and Serere) for 3 seasons. The Area Under Disease Progress Curve combined with 7523 high quality SNPs were analyzed to establish marker-trait associations (MTAs). Genome-Wide Association Studies based on Enriched Compressed Mixed Linear Model detected 32 MTAs at Nakabango: 21 on chromosome A04, 10 on B04 and 1 on B08. Two of the significant markers were localised on the exons of a putative TIR-NBS-LRR disease resistance gene on chromosome A04. Our results suggest the likely involvement of major genes in the resistance to GRD but will need to be further validated with more comprehensive phenotypic and genotypic datasets. The markers identified in the current study will be developed into routine assays and validated for future genomics-assisted selection for GRD resistance in groundnut.

Empathic pain observation does not influence automatic imitation in an online setting.

Previous research has shown that empathic pain observation can lead to motor facilitation in the form of faster reaction times. However, it is unclear whether participants are focusing on the others' pain or simply focusing on their own discomfort/distress (from watching the videos) during the task. This is an important issue as self- vs other-oriented focusing plays a key role in empathic processing. To address this issue, we combined empathic pain observation with the automatic imitation task (AIT). Previous work has shown that AIT effects are smaller after experiencing pain, which has been interpreted as the result of the experience of pain leading to a self-oriented focus. If empathic pain observation similarly leads to a self-oriented focus, then we should expect similar AIT results after pain observation (smaller AIT effects); however, if it instead leads to an other-oriented focus, then we should see the opposite (larger AIT effects). Although we found initial evidence for the latter hypothesis (Experiment 1), subsequent failed replications suggests that we do not have sufficient evidence to claim that pain observation influences automatic imitation one way or the other (Experiment 2 and 3). We discuss some possible reasons for finding null results in these experiments and suggest future avenues of research to better elucidate this topic.

Inequalities in the burden of non-communicable diseases across European countries: a systematic analysis of the Global Burden of Disease 2019 study.

BACKGROUND: Although overall health status in the last decades improved, health inequalities due to non-communicable diseases (NCDs) persist between and within European countries. There is a lack of studies giving insights into health inequalities related to NCDs in the European Economic Area (EEA) countries. Therefore, the aim of the present study was to quantify health inequalities in age-standardized disability adjusted life years (DALY) rates for NCDs overall and 12 specific NCDs across 30 EEA countries between 1990 and 2019. Also, this study aimed to determine trends in health inequalities and to identify those NCDs where the inequalities were the highest. METHODS: DALY rate ratios were calculated to determine and compare inequalities between the 30 EEA countries, by sex, and across time. Annual rate of change was used to determine the differences in DALY rate between 1990 and 2019 for males and females. The Gini Coefficient (GC) was used to measure the DALY rate inequalities across countries, and the Slope Index of Inequality (SII) to estimate the average absolute difference in DALY rate across countries. RESULTS: Between 1990 and 2019, there was an overall declining trend in DALY rate, with larger declines among females compared to males. Among EEA countries, in 2019 the highest NCD DALY rate for both sexes were observed for Bulgaria. For the whole period, the highest DALY rate ratios were identified for digestive diseases, diabetes and kidney diseases, substance use disorders, cardiovascular diseases (CVD), and chronic respiratory diseases - representing the highest inequality between countries. In 2019, the highest DALY rate ratio was found between Bulgaria and Iceland for males. GC and SII indicated that the highest inequalities were due to CVD for most of the study period - however, overall levels of inequality were low. CONCLUSIONS: The inequality in level 1 NCDs DALYs rate is relatively low among all the countries. CVDs, digestive diseases, diabetes and kidney diseases, substance use disorders, and chronic respiratory diseases are the NCDs that exhibit higher levels of inequality across countries in the EEA. This might be mitigated by applying tailored preventive measures and enabling healthcare access.

Anatomical and functional outcomes after bilateral sacrospinous colposuspension (BSC) for the treatment of female genital prolapse.

BACKGROUND: Pelvic organ prolapse is a bothersome condition affecting many women at advanced age, but also frequently observed in young women with certain risk factors. Various surgical techniques have been developed with the aim of providing effective surgical treatment for apical prolapse. The vaginal bilateral sacrospinous colposuspension surgery (BSC) with ultralight mesh and utilization of the i- stich is a relatively new minimal invasive technique with very promising outcomes. The technique offers apical suspension, in the presence or absence of the uterus. The objective of this study is to evaluate the anatomical and functional outcomes of bilateral sacrospinous colposuspension with ultralight mesh in 30 Patients treated with the vaginal single incision standardized technique. METHODS: In this retrospective study, 30 patients were treated by BSC for significant vaginal, uterovaginal or cervical prolapse. A simultaneous anterior colporrhaphy, posterior colporrhaphy or both were performed when indicated. Anatomical and functional outcomes were assessed 1 year postoperatively using the Pelvic Organ Prolapse Quantification system (POP-Q) and the standardised Prolapse Quality of Life (P-QOL) questionnair. RESULTS: The POP-Q parameters were significantly improved at twelve months after surgery compared to baseline. The total score and all four subdomains of the P-QOL-questionnaire showed positive trends and improvement at twelve months after surgery when compared to preoperative values. All patients were asymptomatic and expressed high satisfaction one year after surgery. No intraoperative adverse events were recorded for all patients. Only minimal postoperative complications were recorded and they all resolved completely with conservative management. CONCLUSION: This study highlights the functional and anatomical outcomes of the minimally invasive vaginal bilateral sacrospinal colposuspension with ultralight mesh for the management of apical prolapse. The one year postoperative results of the proposed procedure reflect excellent outcomes with minimal complications. The data published here are very promising and warrant further investigations and more studies to evaluate the long-term outcomes of BSC in the surgical management of apical defects. TRIAL REGISTRATION: The study protocol was approved by the Ethics Committee at the University Hospital of Cologne, Germany (Date of registration: 08.02.2022) (Registration number: 21-1494-retro) (retrospectively registered).

Models of the Translation Process and the Free Energy Principle.

Translation process research (TPR) has generated a large number of models that aim at explaining human translation processes. In this paper, I suggest an extension of the monitor model to incorporate aspects of relevance theory (RT) and to adopt the free energy principle (FEP) as a generative model to elucidate translational behaviour. The FEP-and its corollary, active inference-provide a general, mathematical framework to explain how organisms resist entropic erosion so as to remain within their phenotypic bounds. It posits that organisms reduce the gap between their expectations and observations by minimising a quantity called free energy. I map these concepts on the translation process and exemplify them with behavioural data. The analysis is based on the notion of translation units (TUs) which exhibit observable traces of the translator's epistemic and pragmatic engagement with their translation environment, (i.e., the text) that can be measured in terms of translation effort and effects. Sequences of TUs cluster into translation states (steady state, orientation, and hesitation). Drawing on active inference, sequences of translation states combine into translation policies that reduce expected free energy. I show how the notion of free energy is compatible with the concept of relevance, as developed in RT, and how essential concepts of the monitor model and RT can be formalised as deep temporal generative models that can be interpreted under a representationalist view, but also support a non-representationalist account.

Nudging the N170 forward with prior stimulation-Bridging the gap between N170 and recognition potential.

Evoked response potentials are often divided up into numerous components, each with their own body of literature. But is there less variety than we might suppose? In this study, we nudge one component into looking like another. Both the N170 and recognition potential (RP) are N1 components in response to familiar objects. However, the RP is often measured with a forward mask that ends at stimulus onset whereas the N170 is often measured with no masking at all. This study investigates how inter-stimulus interval (ISI) may delay and distort the N170 into an RP by manipulating the temporal gap (ISI) between forward mask and target. The results revealed reverse relationships between the ISI on the one hand, and the N170 latency, single-trial N1 jitter (an approximation of N1 width) and reaction time on the other hand. Importantly, we find that scalp topographies have a unique signature at the N1 peak across all conditions, from the longest gap (N170) to the shortest (RP). These findings prove that the mask-delayed N1 is still the same N170, even under conditions that are normally associated with a different component like the RP. In general, our results suggest greater synthesis in the study of event related potential components.

Triple blockade of Ido-1, PD-L1 and MEK as a potential therapeutic strategy in NSCLC.

BACKGROUND: Despite the recent progress in the treatment and outcome of Non Small Cell Lung Cancer (NSCLC), immunotherapy has still significant limitations reporting a significant proportion of patients not benefiting from therapy, even in patients with high PD-L1 expression. We have previously demonstrated that the combined inhibition of MEK and PD-L1 in NSCLC patients derived three dimensional cultures exerted significant synergistic effect in terms of immune-dependent cancer cell death. However, subsequent experiments analyzing the expression of Indoleamine 2,3-dioxygenase-1 (Ido-1) gene expression demonstrated that Ido-1 resulted unaffected by the MEK inhibition and even increased after the combined inhibition of MEK and PD-L1 thus representing a potential escape mechanism to this combination. METHODS: We analyzed transcriptomic profile of NSCLC lung adenocarcinoma cohort of TCGA (The Cancer Genome Atlas), stratifying tumors based on EMT (Epithelial mesenchymal Transition) score; in parallel, we investigated the activation of Ido-1 pathway and modulation of immune cytokines productions both in NSCLC cells lines, in peripheral blood mononuclear cells (PBMCs) and in ex-vivo NSCLC spheroids induced by triple inhibition with an anti-PD-L1 monoclonal antibody, the MEK inhibitor and the Ido-1 inhibitor. RESULTS: In NSCLC lung adenocarcinoma patient cohort (from TCGA) Ido-1 gene expression was significantly higher in samples classified as mesenchymal according EMT score. Similarly, on a selected panel of NSCLC cell lines higher expression of MEK and Ido-1 related genes was detected in cells with mesenchymal phenotype according EMT score, thus suggesting a potential correlation of co-activation of these two pathways in the context of EMT, with cancer cells sustaining an immune-suppressive microenvironment. While exerting an antitumor activity, the dual blockade of MEK and PD-L1 enhances the secretion of pro-inflammatory cytokines (IFNγ, TNFα, IL-12 and IL-6) and, consequently, the expression of new immune checkpoints such as Ido-1. The triple inhibition with an anti-PD-L1 monoclonal antibody, the MEK inhibitor and the Ido-1 inhibitor demonstrated significant antiproliferative and proapoptotic activity on ex-vivo NSCLC samples; at the same time the triple combination kept increased the levels of pro-inflammatory cytokines produced by both PBMCs and tumor spheroids in order to sustain the immune response and simultaneously decreased the expression of other checkpoint (such as CTLA-4, Ido-1 and TIM-3) thus promoting an immune-reactive and inflamed micro-environment. CONCLUSIONS: We show that Ido-1 activation is a possible escape mechanism to immune-mediated cell death induced by combination of PD-L1 and MEK inhibitors: also, we show that triple combination of anti-PD-L1, anti-MEK and anti-Ido-1 drugs may overcome this negative feedback and restore anti-tumor immune response in NSCLC patients' derived three dimensional cultures.

Early transcriptome changes induced by the Geminivirus C4 oncoprotein: setting the stage for oncogenesis.

BACKGROUND: The Beet curly top virus C4 oncoprotein is a pathogenic determinant capable of inducing extensive developmental abnormalities. No studies to date have investigated how the transcriptional profiles differ between plants expressing or not expressing the C4 oncoprotein. RESULTS: We investigated early transcriptional changes in Arabidopsis associated with expression of the Beet curly top virus C4 protein that represent initial events in pathogenesis via a comparative transcriptional analysis of mRNAs and small RNAs. We identified 48 and 94 differentially expressed genes at 6- and 12-h post-induction versus control plants. These early time points were selected to focus on direct regulatory effects of C4 expression. Since previous evidence suggested that the C4 protein regulated the brassinosteroid (BR)-signaling pathway, differentially expressed genes could be divided into two groups: those responsive to alterations in the BR-signaling pathway and those uniquely responsive to C4. Early transcriptional changes that disrupted hormone homeostasis, 18 and 19 differentially expressed genes at both 6- and 12-hpi, respectively, were responsive to C4-induced regulation of the BR-signaling pathway. Other C4-induced differentially expressed genes appeared independent of the BR-signaling pathway at 12-hpi, including changes that could alter cell development (4 genes), cell wall homeostasis (5 genes), redox homeostasis (11 genes) and lipid transport (4 genes). Minimal effects were observed on expression of small RNAs. CONCLUSION: This work identifies initial events in genetic regulation induced by a geminivirus C4 oncoprotein. We provide evidence suggesting the C4 protein regulates multiple regulatory pathways and provides valuable insights into the role of the C4 protein in regulating initial events in pathogenesis.

To move or not to move: motor cortical output is enhanced during pain observation regardless of motor preparation state.

Previous transcranial magnetic stimulation (TMS) studies have reported a decrease in motor cortical output during pain observation. In contrast, recent behavioral studies have shown that response times are faster after pain observation. This suggests that there is a mismatch between motor activity "during" versus "after" pain observation. We propose that these opposing effects of pain observation on motor activity may be explained by task constraints, as participants in TMS studies are instructed to keep still and relax their hands, whereas participants in behavioral studies maintain a state of readiness to respond. Task and methodological differences make it difficult to compare the results from TMS and behavioral paradigms examining the motor consequences of pain observation. As such, the aim of the current study is to directly test whether task instructions affect motor activity in TMS and behavioral measures of motor activity in the context of pain observation, within a single experiment. Participants watched videos of hands in painful versus nonpainful scenarios while TMS-induced motor evoked potentials were recorded. In the "active" block, participants responded to a cue that appeared immediately after each video; in the "passive" block, they relaxed their hand. Contrary to expectations, participants showed enhanced motor cortical output during pain observation (vs. no-pain) in "both" blocks. We discuss these results in relation to the wider literature on the social neuroscience of empathy.NEW & NOTEWORTHY The current study provides novel results showing an increase motor cortical output, measured via transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs), during empathic pain observation regardless of motor preparation state. Interestingly, this finding runs counter to the empathy for pain literature, which often finds a decrease in motor cortical output during empathic pain observation. We discuss potential explanations for this discrepancy and relate these results to the wider empathy for pain literature.

A wake-up call for cancer DNA damage: the role of Schlafen 11 (SLFN11) across multiple cancers.

DNA-damaging agents exploit increased genomic instability, a hallmark of cancer. Recently, inhibitors targeting the DNA damage response (DDR) pathways, such as PARP inhibitors, have also shown promising therapeutic potential. However, not all tumors respond well to these treatments, suggesting additional determinants of response are required. Schlafen 11 (SLFN11), a putative DNA/RNA helicase that induces irreversible replication block, is emerging as an important regulator of cellular response to DNA damage. Preclinical and emerging clinical trial data suggest that SLFN11 is a predictive biomarker of response to a wide range of therapeutics that cause DNA damage including platinum salts and topoisomerase I/II inhibitors, as well as PARP inhibitors, which has raised exciting possibilities for its clinical application. In this article, we review the function, prevalence, and clinical testing of SLFN11 in tumor biopsy samples and circulating tumor cells. We discuss mounting evidence of SLFN11 as a key predictive biomarker for a wide range of cancer therapeutics and as a prognostic marker across several cancer types. Furthermore, we discuss emerging areas of investigation such as epigenetic reactivation of SLFN11 and its role in activating immune response. We then provide perspectives on open questions and future directions in studying this important biomarker.

Ultrashort echo time Cones double echo steady state (UTE-Cones-DESS) for rapid morphological imaging of short T2 tissues.

PURPOSE: In this study, we aimed to develop a new technique, ultrashort echo time Cones double echo steady state (UTE-Cones-DESS), for highly efficient morphological imaging of musculoskeletal tissues with short T2 s. We also proposed a novel, single-point Dixon (spDixon)-based approach for fat suppression. METHODS: The UTE-Cones-DESS sequence was implemented on a 3T MR system. It uses a short radiofrequency (RF) pulse followed by a pair of balanced spiral-out and spiral-in readout gradients separated by an unbalanced spoiling gradient in-between. The readout gradients are applied immediately before or after the RF pulses to achieve a UTE image (S+ ) and a spin/stimulated echo image (S- ). Weighted echo subtraction between S+ and S- was performed to achieve high contrast specific to short T2 tissues, and spDixon was applied to suppress fat by using the intrinsic complex signal of S+ and S- . Six healthy volunteers and five patients with osteoarthritis were recruited for whole-knee imaging. Additionally, two healthy volunteers were recruited for lower leg imaging. RESULTS: The UTE-Cones-DESS sequence allows fast volumetric imaging of musculoskeletal tissues with excellent image contrast for the osteochondral junction, tendons, menisci, and ligaments in the knee joint as well as cortical bone and aponeurosis in the lower leg within 5 min. spDixon yields efficient fat suppression in both S+ and S- images without requiring any additional acquisitions or preparation pulses. CONCLUSION: The rapid UTE-Cones-DESS sequence can be used for high contrast morphological imaging of short T2 tissues, providing a new tool to assess their association with musculoskeletal disorders.

High contrast cartilaginous endplate imaging using a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence.

Ultrashort echo time (UTE) sequences can image tissues with transverse T 2 /T 2 * relaxations too short to be efficiently observed on routine clinical MRI sequences, such as the vertebral body cartilaginous endplate (CEP). Here, we describe a 3D adiabatic inversion-recovery-prepared fat-saturated ultrashort echo time (3D IR-FS-UTE) sequence to highlight the CEP of vertebral bodies in comparison to the intervertebral disc (IVD) and bone marrow fat (BF) at 3 T. The IR-FS-UTE sequence used a 3D UTE sequence combined with an adiabatic IR preparation pulse centered in the middle of the water and fat peaks, while a fat saturation module was used to suppress the signal from fat. A slab-selective half pulse was used for signal excitation, and a 3D center-out cones trajectory was used for more efficient data sampling. The 3D IR-FS-UTE sequence was applied to an ex vivo human spine sample, as well as the spines of six healthy volunteers and of three patients with back pain. Bright continuous lines representing signal from CEP were found in healthy IVDs. The measured contrast-to-noise ratio was 18.5 ± 4.9 between the CEP and BF, and 20.3 ± 4.15 between the CEP and IVD for the six volunteers. Abnormal IVDs showed CEP discontinuity or irregularity in the sample and patient studies. In conclusion, the proposed 3D IR-FS-UTE sequence is feasible for imaging the vertebral body's CEP in vivo with high contrast.

Diffusion-weighted double-echo steady-state with a three-dimensional cones trajectory for non-contrast-enhanced breast MRI.

The image quality limitations of echo-planar diffusion-weighted imaging (DWI) are an obstacle to its widespread adoption in the breast. Steady-state DWI is an alternative DWI method with more robust image quality but its contrast for imaging breast cancer is not well-understood. The aim of this study was to develop and evaluate diffusion-weighted double-echo steady-state imaging with a three-dimensional cones trajectory (DW-DESS-Cones) as an alternative to conventional DWI for non-contrast-enhanced MRI in the breast. This prospective study included 28 women undergoing clinically indicated breast MRI and six asymptomatic volunteers. In vivo studies were performed at 3 T and included DW-DESS-Cones, DW-DESS-Cartesian, DWI, and CE-MRI acquisitions. Phantom experiments (diffusion phantom, High Precision Devices) and simulations were performed to establish framework for contrast of DW-DESS-Cones in comparison to DWI in the breast. Motion artifacts of DW-DESS-Cones were measured with artifact-to-noise ratio in volunteers and patients. Lesion-to-fibroglandular tissue signal ratios were measured, lesions were categorized as hyperintense or hypointense, and an image quality observer study was performed in DW-DESS-Cones and DWI in patients. Effect of DW-DESS-Cones method on motion artifacts was tested by mixed-effects generalized linear model. Effect of DW-DESS-Cones on signal in phantom was tested by quadratic regression. Correlation was calculated between DW-DESS-Cones and DWI lesion-to-fibroglandular tissue signal ratios. Inter-observer agreement was assessed with Gwet's AC. Simulations predicted hyperintensity of lesions with DW-DESS-Cones but at a 3% to 67% lower degree than with DWI. Motion artifacts were reduced with DW-DESS-Cones versus DW-DESS-Cartesian (p < 0.05). Lesion-to-fibroglandular tissue signal ratios were not correlated between DW-DESS-Cones and DWI (r = 0.25, p = 0.38). Concordant hyperintensity/hypointensity was observed between DW-DESS-Cones and DWI in 11/14 lesions. DW-DESS-Cones improved sharpness, distortion, and overall image quality versus DWI. DW-DESS-Cones may be able to eliminate motion artifacts in the breast allowing for investigation of higher degrees of steady-state diffusion weighting. Malignant breast lesions in DW-DESS-Cones demonstrated hyperintensity with respect to surrounding tissue without an injection of contrast. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 1.

Investigating the effects of pain observation on approach and withdrawal actions.

Previous research has shown that observing another individual receiving a painful stimulus leads to motor facilitation as indexed by faster reaction times. The current study explores whether the type of action that is executed modulates this facilitation effect. Specifically, we examined whether approach-like and withdraw-like movements are differentially influenced by pain observation. In experiment 1, participants performed key presses (approach) and releases (withdraw) after observing another person in pain (vs. no pain). In experiment 2, participants used a joystick to make forward (approach) and backward (withdraw) movements after observing another person in pain (vs. no pain). Across both experiments, we did not find evidence for differential effects of pain observation on approach-like and withdraw-like movements. We do, however, report a robust response-general effect of pain observation on motor behaviour (i.e., faster reaction times after pain observation vs. no pain, regardless of movement type). We discuss these results in relation to the wider emotion, attention, and social neuroscience of empathy literatures.

Studying sense of agency online: Can intentional binding be observed in uncontrolled online settings?

Intentional binding is often used as an implicit index of the sense of agency. However, intentional binding research has primarily been conducted in controlled lab environments. During the COVID-19 global pandemic, there has been a shift to implementing studies using online platforms and it is an open question whether the intentional binding effect can be found using an online experimental set-up and participant sample. Here, we address this question by asking online participants to complete the Libet clock version of the intentional binding task, which we make freely available to researchers as a jsPsych (De Leeuw, 2014) plugin. Intentional binding was observed in the form of later keypress estimates and earlier auditory tone estimates, when the auditory tone followed the keypress. These findings confirm that intentional binding can be assessed in online contexts. We discuss these findings in relation to the broader intentional binding literature.

Inversion recovery UTE based volumetric myelin imaging in human brain using interleaved hybrid encoding.

PURPOSE: Direct myelin imaging can improve the characterization of myelin-related diseases such as multiple sclerosis. In this study, we explore a novel method to directly image myelin using inversion recovery-prepared hybrid encoding (IR-HE) UTE MRI. METHODS: The IR-HE sequence uses an adiabatic inversion pulse to suppress the long T2 white matter signal, followed by 3D dual-echo HE utilizing both single point imaging and radial frequency encoding, for which the subtraction image between 2 echoes reveals the myelin signal with high contrast. To reduce scan time, it is common to obtain multiple spokes per IR. Here, we invented a novel method to improve the HE, adapted for the multi-spoke IR imaging-termed interleaved HE-for which single point imaging encoding is interleaved between radial frequency encodings near nulling point to allow more efficient IR-signal suppression. To evaluate the proposed approach, a computer simulation, myelin phantom experiment, an ex vivo experiment with a cadaveric multiple sclerosis brain, and an in vivo experiment with 8 healthy volunteers and 13 multiple sclerosis patients were performed. RESULTS: The computer simulation showed that IR-interleaved HE allows for improved contrast of myelin signal with reduced imaging artifacts. The myelin phantom experiment showed IR-interleaved HE allows direct imaging of myelin lipid with excellent suppression of water signal. In the ex vivo and in vivo experiments, the proposed method demonstrated highly specific imaging of myelin in white matter of the brain. CONCLUSION: IR-interleaved HE allows for time-efficient, high-contrast direct myelin imaging and can detect demyelinated lesions in multiple sclerosis patients.

Fast quantitative three-dimensional ultrashort echo time (UTE) Cones magnetic resonance imaging of major tissues in the knee joint using extended sprial sampling.

The purpose of this study is to investigate the effect of extending the spiral sampling window on quantitative 3D ultrashort echo time (UTE) Cones imaging of major knee joint tissues including articular cartilage, menisci, tendons and ligaments at 3 T. Nine cadaveric human whole knee specimens were imaged on a 3 T clinical MRI scanner. A series of quantitative 3D UTE Cones imaging biomarkers including T2 *, T1 , adiabatic T1ρ , magnetization transfer ratio (MTR) and macromolecular fraction (MMF) were estimated using spiral sampling trajectories with various durations. Errors in UTE MRI biomarkers as a function of sampling time were evaluated using a nonstretched spiral trajectory as a reference standard. No significant differences were observed by increasing the spiral sampling window from 1116 to 2232 µs in the calculated T2 *, T1 , adiabatic T1ρ , MTR and MMF, as all P-values were over .05 as assessed by ANOVA with two-sided Dunnett's test. Although extending the sampling window results in signal loss for short T2 components, there was limited effect on the calculated quantitative biomarkers, with error percentages typically smaller than 5% in all the evaluated tissues. The total scan time can be reduced by up to 54% with quantification errors of less than 5% in any evaluated major tissue in the knee joint, suggesting that 3D UTE Cones MRI techniques can be greatly accelerated by using a longer spiral sampling window without causing additional quantitative bias.