Protocol for a randomised controlled unblinded feasibility trial of HD-DRUM: a rhythmic movement training application for cognitive and motor symptoms in people with Huntington's disease.

INTRODUCTION: Huntington's disease (HD) is an inherited neurodegenerative disease causing progressive cognitive and motor decline, largely due to basal ganglia (BG) atrophy. Rhythmic training offers promise as therapy to counteract BG-regulated deficits. We have developed HD-DRUM, a tablet-based app to enhance movement synchronisation skills and improve cognitive and motor abilities in people with HD. This paper outlines a randomised controlled unblinded trial protocol to determine the feasibility of a larger effectiveness trial for HD-DRUM. Additionally, the trial investigates cognitive and motor function measures, along with brain microstructure, aiming to advance our understanding of the neural mechanisms underlying training effects. METHODS, DESIGN AND ANALYSIS: 50 individuals with HD, confirmed by genetic testing, and a Total Functional Capacity (TFC) score of 9-13, will be recruited into a two-arm randomised controlled feasibility trial. Consenting individuals with HD will be randomised to the intervention group, which entails 8 weeks of at-home usage of HD-DRUM or a usual-activity control group. All participants will undergo cognitive and motor assessments, alongside ultra-strong gradient (300 mT/m) brain microstructural MRI before and after the 8-week period. The feasibility assessment will encompass recruitment, retention, adherence and acceptability of HD-DRUM following prespecified criteria. The study will also evaluate variations in cognitive and motor performance and brain microstructure changes resulting from the intervention to determine effect size estimates for future sample size calculations. ETHICS AND DISSEMINATION: The study has received favourable ethical opinion from the Wales Research Ethics Committee 2 (REC reference: 22/WA/0147) and is sponsored by Cardiff University (SPON1895-22) (Research Integrity, Governance and Ethics Team, Research & Innovation Services, Cardiff University, second Floor, Lakeside Building, University Hospital of Wales, Cardiff, CF14 4XW). Findings will be disseminated to researchers and clinicians in peer-reviewed publications and conference presentations, and to participants, carers and the general public via newsletters and public engagement activities. Data will be shared with the research community via the Enroll-HD platform. TRIAL REGISTRATION NUMBER: ISRCTN11906973.

Intraoperative margin assessment with near real time pathology during partial gland ablation of prostate cancer: A feasibility study.

BACKGROUND: In-field or in-margin recurrence after partial gland cryosurgical ablation (PGCA) of prostate cancer (PCa) remains a limitation of the paradigm. Stimulated Raman histology (SRH) is a novel microscopic technique allowing real time, label-free, high-resolution microscopic images of unprocessed, un-sectioned tissue which can be interpreted by humans or artificial intelligence (AI). We evaluated surgical team and AI interpretation of SRH for real-time pathologic feedback in the planning and treatment of PCa with PGCA. METHODS: About 12 participants underwent prostate mapping biopsies during PGCA of their PCa between January and June 2022. Prostate biopsies were immediately scanned in a SRH microscope at 20 microns depth using 2 Raman shifts to create SRH images which were interpreted by the surgical team intraoperatively to guide PGCA, and retrospectively assessed by AI. The cores were then processed, hematoxylin and eosin stained as per normal pathologic protocols and used for ground truth pathologic assessment. RESULTS: Surgical team interpretation of SRH intraoperatively revealed 98.1% accuracy, 100% sensitivity, 97.3% specificity for identification of PCa, while AI showed a 97.9% accuracy, 100% sensitivity and 97.5% specificity for identification of clinically significant PCa. 3 participants' PGCA treatments were modified after SRH visualized PCa adjacent to an expected MRI predicted tumor margin or at an untreated cryosurgical margin. CONCLUSION: SRH allows for accurate rapid identification of PCa in PB by a surgical team interpretation or AI. PCa tumor mapping and margin assessment during PGCA appears to be feasible and accurate. Further studies evaluating impact on clinical outcomes are warranted.

MRI signatures of cortical microstructure in human development align with oligodendrocyte cell-type expression.

Neuroanatomical changes to the cortex during adolescence have been well documented using MRI, revealing ongoing cortical thinning and volume loss with age. However, the underlying cellular mechanisms remain elusive with conventional neuroimaging. Recent advances in MRI hardware and new biophysical models of tissue informed by diffusion MRI data hold promise for identifying the cellular changes driving these morphological observations. This study used ultra-strong gradient MRI to obtain high-resolution, in vivo estimates of cortical neurite and soma microstructure in sample of typically developing children and adolescents. Cortical neurite signal fraction, attributed to neuronal and glial processes, increased with age (mean R2 fneurite=.53, p<3.3e-11, 11.91% increase over age), while apparent soma radius decreased (mean R2 Rsoma=.48, p<4.4e-10, 1% decrease over age) across domain-specific networks. To complement these findings, developmental patterns of cortical gene expression in two independent post-mortem databases were analysed. This revealed increased expression of genes expressed in oligodendrocytes, and excitatory neurons, alongside a relative decrease in expression of genes expressed in astrocyte, microglia and endothelial cell-types. Age-related genes were significantly enriched in cortical oligodendrocytes, oligodendrocyte progenitors and Layer 5-6 neurons (pFDR<.001) and prominently expressed in adolescence and young adulthood. The spatial and temporal alignment of oligodendrocyte cell-type gene expression with neurite and soma microstructural changes suggest that ongoing cortical myelination processes contribute to adolescent cortical development. These findings highlight the role of intra-cortical myelination in cortical maturation during adolescence and into adulthood.

White Matter Microstructural Changes Using Ultra-Strong Diffusion Gradient MRI in Adult-Onset Idiopathic Focal Cervical Dystonia.

BACKGROUND AND OBJECTIVES: Adult-onset idiopathic focal cervical dystonia (AOIFCD) involves abnormal posturing of the cervical musculature and, in some individuals, an associated head tremor. Existing neuroimaging studies have implicated key motor networks. However, measures used to date lack specificity toward underlying pathophysiologic differences. We aim to assess white matter motor pathways for localized, microstructural differences, which may aid in understanding underlying mechanisms. METHODS: Individuals diagnosed with AOIFCD and an age- and sex-matched control group were prospectively recruited through the Welsh Movement Disorders Research Network. All participants underwent in-depth clinical phenotyping and MRI (structural and diffusion sequences) using ultra-strong diffusion gradients. Tractography (whole-tract median values) and tractometry (along tract profiling) were performed for key white matter motor pathways assessing diffusion kurtosis imaging (DKI), neurite orientation dispersion and density imaging (NODDI), and standard model parameters. Groups were compared using linear model analysis with Bonferroni multiple comparison correction. RESULTS: Fifty participants with AOIFCD and 30 healthy control participants were recruited, with 46 with AOIFCD and 30 healthy controls included for analysis (33 without head tremor, 13 with head tremor). Significant differences were observed in the anterior thalamic radiations (lower mid-tract fractional anisotropy [estimate = -0.046, p = 3.07 × 10-3], radial kurtosis [estimate = -0.165, p = 1.42 × 10-4], f-intra-axonal signal fraction [estimate = -0.044, p = 2.78 × 10-3], p2 orientation coherence [estimate = -0.043, p = 1.64 × 10-3], higher Orientation Dispersion Index [ODI, estimate = 0.023, p = 2.22 × 10-3]) and thalamopremotor tracts (higher mid-tract mean kurtosis [estimate = 0.064, p = 7.56 × 10-4], lower Neurite Density Index [estimate = 0.062, p = 2.1 × 10-3], higher distal tract ODI [estimate = 0.062, p = 3.1 × 10-3], lower f [estimate = -0.1, p = 2.3 × 10-3], and striatopremotor tracts [proximal lower f: estimate = -0.075, p = 1.06 × 10-3]). These measures correlated with clinical measures: dystonia duration (right thalamopremotor distal ODI: r = -0.9, p = 1.29 × 10-14), psychiatric symptoms (obsessive compulsive symptoms: left anterior thalamic radiation p2 r = 0.92, p = 2.797 × 10-11), sleep quality (Sleep Disorders Questionnaire Score: left anterior thalamic radiation ODI: r = -0.84, p = 4.84 × 10-11), pain (left anterior thalamic radiation ODI: r = -0.89, p = 1.4 × 10-13), and cognitive functioning (paired associated learning task p2, r = 0.94, p = 6.68 × 10-20). DISCUSSION: Overall, localized microstructural differences were identified within tracts linking the prefrontal and premotor cortices with thalamic and basal ganglia regions, suggesting pathophysiologic processes involve microstructural aberrances of motor system modulatory pathways, particularly involving intra-axonal and fiber orientation dispersion measures.

Probabilistic Finite Element Analysis of Human Rib Biomechanics: A Framework for Improved Generalizability.

In dynamic impact events, thoracic injuries often involve rib fractures, which are closely related to injury severity. Previous studies have investigated the behavior of isolated ribs under impact loading conditions, but often neglected the variability in anatomical shape and tissue material properties. In this study, we used probabilistic finite element analysis and statistical shape modeling to investigate the effect of population-wide variability in rib cortical bone tissue mechanical properties and rib shape on the biomechanical response of the rib to impact loading. Using the probabilistic finite element analysis results, a response surface model was generated to rapidly investigate the biomechanical response of an isolated rib under dynamic anterior-posterior load given the variability in rib morphometry and tissue material properties. The response surface was used to generate pre-fracture force-displacement computational corridors for the overall population and a population sub-group of older mid-sized males. When compared to the experimental data, the computational mean response had a RMSE of 4.28N (peak force 94N) and 6.11N (peak force 116N) for the overall population and sub-group respectively, whereas the normalized area metric when comparing the experimental and computational corridors ranged from 3.32% to 22.65% for the population and 10.90% to 32.81% for the sub-group. Furthermore, probabilistic sensitivities were computed in which the contribution of uncertainty and variability of the parameters of interest was quantified. The study found that rib cortical bone elastic modulus, rib morphometry and cortical thickness are the random variables that produce the largest variability in the predicted force-displacement response. The proposed framework offers a novel approach for accounting biological variability in a representative population and has the potential to improve the generalizability of findings in biomechanical studies.

Why do students choose to do an extended GP placement?

The drivers for medical students' decision making when considering which Student Selected Component (SSC) to undertake is poorly understood. Furthermore, it is unclear why students undertake a specific SSC allowing them to have an extended placement in GP in their final year. It is known that high quality GP placements encourage students to subsequently choose GP as their career, therefore if the decision-making process of students in this area can be better understood, then this may help inform medical school actions to encourage a greater uptake of these extended placements.Semi-structured interviews were conducted with final year medical students at a Scottish University. Students were selected to provide a mixture of those who had and had not chosen to undertake the extended placement. The data was transcribed and analysed using thematic analysis to generate themes which represented the data.This showed that career intention was a major factor driving SSC choice. Additionally, students sought peer feedback and tended to avoid specific SSCs if they felt a lack of internal motivation. Considering the choice for the extended placement, students tended, again, to choose based on career intentions, and they also based their decision on previous experiences of GP.Career intention and prior experience are key factors in student choice of SSC and whether to undertake an extended GP. In order to address the national shortage of GPs medical schools need to consider how they might influence these drivers.

Investigating the Impact of Blunt Force Trauma: A Probabilistic Study of Behind Armor Blunt Trauma Risk.

Evaluating Behind Armor Blunt Trauma (BABT) is a critical step in preventing non-penetrating injuries in military personnel, which can result from the transfer of kinetic energy from projectiles impacting body armor. While the current NIJ Standard-0101.06 standard focuses on preventing excessive armor backface deformation, this standard does not account for the variability in impact location, thorax organ and tissue material properties, and injury thresholds in order to assess potential injury. To address this gap, Finite Element (FE) human body models (HBMs) have been employed to investigate variability in BABT impact conditions by recreating specific cases from survivor databases and generating injury risk curves. However, these deterministic analyses predominantly use models representing the 50th percentile male and do not investigate the uncertainty and variability inherent within the system, thus limiting the generalizability of investigating injury risk over a diverse military population. The DoD-funded I-PREDICT Future Naval Capability (FNC) introduces a probabilistic HBM, which considers uncertainty and variability in tissue material and failure properties, anthropometry, and external loading conditions. This study utilizes the I-PREDICT HBM for BABT simulations for three thoracic impact locations-liver, heart, and lower abdomen. A probabilistic analysis of tissue-level strains resulting from a BABT event is used to determine the probability of achieving a Military Combat Incapacitation Scale (MCIS) for organ-level injuries and the New Injury Severity Score (NISS) is employed for whole-body injury risk evaluations. Organ-level MCIS metrics show that impact at the heart can cause severe injuries to the heart and spleen, whereas impact to the liver can cause rib fractures and major lacerations in the liver. Impact at the lower abdomen can cause lacerations in the spleen. Simulation results indicate that, under current protection standards, the whole-body risk of injury varies between 6 and 98% based on impact location, with the impact at the heart being the most severe, followed by impact at the liver and the lower abdomen. These results suggest that the current body armor protection standards might result in severe injuries in specific locations, but no injuries in others.

The I-PREDICT 50th Percentile Male Warfighter Finite Element Model: Development and Validation of the Thoracolumbar Spine.

Military personnel are commonly at risk of lower back pain and thoracolumbar spine injury. Human volunteers and postmortem human subjects have been used to understand the scenarios where injury can occur and the tolerance of the warfighter to these loading regimes. Finite element human body models (HBMs) can accurately simulate the mechanics of the human body and are a useful tool for understanding injury. In this study, a HBM thoracolumbar spine was developed and hierarchically ï»¿validated as part of the Incapacitation Prediction for Readiness in Expeditionary Domains: an Integrated Computational Tool (I-PREDICT) program. Constitutive material models were sourced from literature and the vertebrae and intervertebral discs were hexahedrally meshed from a 50th percentile male CAD dataset. Ligaments were modeled through attaching beam elements at the appropriate anatomical insertion sites. 94 simulations were replicated from experimental PMHS tests at the vertebral body, functional spinal unit (FSU), and regional lumbar spine levels. The BioRank (BRS) biofidelity ranking system was used to assess the response of the I-PREDICT model. At the vertebral body level, the I-PREDICT model showed good agreement with experimental results. The I-PREDICT FSUs showed good agreement in tension and compression and had comparable stiffness values in flexion, extension, and axial rotation. The regional lumbar spine exhibited "good" biofidelity when tested in tension, compression, extension, flexion, posterior shear, and anterior shear (BRS regional average = 1.05). The validated thoracolumbar spine of the I-PREDICT model can be used to better understand and mitigate injury risk to the warfighter.

Controlled Antenatal Thyroid Screening Study III: Effects of gestational thyroid status on adolescent brain morphology.

CONTEXT: Children born to mothers with gestational hypo- or hyperthyroidism may have increased risk of adverse neurodevelopmental outcomes. However, the effects of maternal thyroid status on offspring brain development are unclear. OBJECTIVE: To establish whether adolescent brain morphology is affected by suboptimal gestational thyroid function (SGTF). DESIGN AND SETTING: The Controlled Antenatal Thyroid Screening (CATS) study randomized mothers with SGTF to levothyroxine or no supplementation from ∼12 weeks' gestation. At age 9, children born to mothers who were over-treated with levothyroxine had a higher risk of conduct and hyperactivity traits. For the current CATS III study, children underwent neuroimaging studies, including T1-weighted structural magnetic resonance imaging (MRI). PARTICIPANTS: A total of 85 children aged 11-16 years had usable T1-weighted MRI data (exposed to untreated SGTF (n=21), normal GTF (n=24), or treated SGTF (optimally-treated (n=21), over-treated (n=20)). MAIN OUTCOME MEASURES: Primary outcome: to examine the association of SGTF and its treatment with global brain volumes. Secondary and exploratory outcomes: to investigate the association of maternal TSH and free T4 levels with global and subregional brain volumes. Results were adjusted for age, sex and pubertal scores. RESULTS: There were no significant differences in global brain volumetric measures between groups, including total gray matter volume (p=0.373). Weak positive correlations were found between maternal TSH, but not FT4, levels and several brain volumes, but these did not survive testing for multiple comparisons. CONCLUSIONS: We found no evidence that SGTF was associated with differences in adolescent brain morphology, and no impact of levothyroxine supplementation.

Update on Blindness From Filler: Review of Prognostic Factors, Management Approaches, and a Century of Published Cases.

BACKGROUND: Vision loss secondary to aesthetic filler treatment is a rare but disastrous complication. OBJECTIVES: The aim was to update the published cases of blindness after filler injection that have occurred since our group published reviews of 98 cases in 2015 and an additional 48 cases in 2019. METHODS: A literature review was performed to identify all cases of visual complications caused by filler injection published between September 2018 and March 2023. The cases were analyzed independently and in combination with previously reviewed cases. Analyses are based on the number of cases with data available. RESULTS: 365 new cases of partial or complete vision loss after filler injection were identified. The sites that were highest risk were the nose (40.6%), forehead (27.7%), and glabella (19.0%). The filler injected was hyaluronic acid in 79.6% of cases. The most common associated signs were ptosis (56.2%), ophthalmoplegia (44.1%), pain (31.2%), and skin changes (73.2%). Stroke-like features were seen in 19.2% of cases. Of the cases reporting visual outcomes (318), 6.0% experienced complete vision recovery, 25.8% had partial improvement in visual acuity, and 68.2% had no vision recovery. Partially preserved visual acuity at onset was a significant predictor of visual improvement (p < .001). The three most common treatments were subcutaneous hyaluronidase at or near the filler site (70.1%), systemic steroids (57.3%), and intra-arterial thrombolytic therapy (56.0%). No treatments were significantly associated with visual improvement (p > .05). CONCLUSIONS: Although blindness and stroke from fillers is a rare complication, practitioners who inject filler should have a thorough knowledge of prevention and management strategies.

"Efficacy and Safety of OnabotulinumtoxinA for the Treatment of Platysma Prominence: A Randomized Phase 2 Dose-Ranging Study".

BACKGROUND: With aging, repetitive contraction of the platysma leads to an increase in platysma prominence (PP) characterized by the accentuation of vertical neck bands and blunting of the jawline's contour. METHODS: This multicenter, double-blind, phase 2 study evaluated onabotulinumtoxinA (onabotA) treatment in adults with Moderate to Severe PP. Participants were randomized to receive 1 treatment of onabotA low dose (LD), onabotA high dose (HD), or placebo, and were followed for 4 months. Efficacy endpoints were the achievement of a ≥ 1-grade improvement on both the left and right sides at Day 14 at maximum contraction as assessed by the investigator (primary) or by participants (secondary) using validated scales. Safety was evaluated throughout. RESULTS: Participants in the modified intent-to-treat population (N = 164) had a mean age of 50 years; 95.1% were female and 93.9% were White. The primary endpoint was met for both onabotA groups, with investigator-assessed ≥ 1-grade improvement in 77.8% (LD) and 88.2% (HD) vs 12.0% (placebo) of participants on Day 14 (P < 0.0001 vs placebo). Based on participant self-assessment, 75.9% (LD) and 88.2% (HD) vs 18.0% (placebo) achieved ≥ 1-grade improvement on Day 14 (P < 0.0001 vs placebo). Most treatment-related adverse events (AEs) were procedure-related, transient, and mild in severity. The most frequent onabotA-related AE was neck muscle weakness, reported in the HD group. CONCLUSIONS: OnabotA was effective in improving the appearance of PP based on both investigators' and participants' ratings. Treatment was well tolerated.

A Multicenter, Randomized, Evaluator-Blinded Study to Examine the Safety and Effectiveness of Hyaluronic Acid Filler in the Correction of Infraorbital Hollows.

BACKGROUND: Hyaluronic acid injections are increasingly used for correction of infraorbital hollows (IOHs). OBJECTIVES: Examination of effectiveness (IOH correction) and safety of Restylane® EyelightTM hyaluronic acid (HAEYE, Galderma, Uppsala, Sweden) injections. METHODS: Subjects with moderate/severe IOHs, assessed using the Galderma infraorbital hollows scale (GIHS), were randomized to HAEYE injections (via needle/cannula) (Day 1+optional Month-1 touch up) or no-treatment control. Primary endpoint was blinded evaluator-reported Month-3 response, defined as ≥1-point GIHS improvement from baseline (both sides, concurrently). Other endpoints examined investigator-reported aesthetic improvement (GAIS), subject-reported satisfaction (FACE-Q™ satisfaction with outcome; satisfaction questionnaire), and adverse events. RESULTS: Overall, 333 subjects were randomized. Month 3 GIHS responder rate was significantly higher with HA-EYE (87.4%) versus control (17.7%; p<0.001), and comparable between HA-EYE-needle and HA-EYE-cannula groups (p=0.967). HAEYE GAIS responder rate was 87.5-97.7% (Months 3-12). Mean FACE-Q Rasch-transformed scores were 64.3-73.5 (HAEYE) versus 14.1-16.2 (control) through Month 12. Subjects reported looking younger (≥71%) and less tired (≥79%) with reduced under-eye shadows (≥76%) and recovered within 3-5 hours, post-treatment. Efficacy was maintained through Month 12 (63.5% GIHS responders) and through Month 18, after Month-12 retreatment (80.3% GIHS responders; 99.4% GAIS responders; FACE-Q scores: 72.5-72.8). Forty subjects (12.7%) reported typically mild adverse events (4.9% HAEYE-needle; 20.9% HAEYE-cannula). CONCLUSION: HAEYE treatment was effective in correcting moderate/severe IOHs at the primary endpoint (Month 3). Efficacy was sustained through Month 12 after first treatment for 63.5% and through Month 18 for 80.3% (after one retreatment) with needle or cannula administration. Safety outcomes were reassuring.

In vivo diffusion MRI of the human heart using a 300 mT/m gradient system.

PURPOSE: This work reports for the first time on the implementation and application of cardiac diffusion-weighted MRI on a Connectom MR scanner with a maximum gradient strength of 300 mT/m. It evaluates the benefits of the increased gradient performance for the investigation of the myocardial microstructure. METHODS: Cardiac diffusion-weighted imaging (DWI) experiments were performed on 10 healthy volunteers using a spin-echo sequence with up to second- and third-order motion compensation ( M 2 $$ {M}_2 $$ and M 3 $$ {M}_3 $$ ) and b = 100 , 450 $$ b=100,450 $$ , and 1000 s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ (twice the b max $$ {b}_{\mathrm{max}} $$ commonly used on clinical scanners). Mean diffusivity (MD), fractional anisotropy (FA), helix angle (HA), and secondary eigenvector angle (E2A) were calculated for b = [100, 450] s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ and b = [100, 1000] s / m m 2 $$ \mathrm{s}/\mathrm{m}{\mathrm{m}}^2 $$ for both M 2 $$ {M}_2 $$ and M 3 $$ {M}_3 $$ . RESULTS: The MD values with M 3 $$ {M}_3 $$ are slightly higher than with M 2 $$ {M}_2 $$ with Δ MD = 0 . 05 ± 0 . 05 [ × 1 0 - 3 mm 2 / s ] ( p = 4 e - 5 ) $$ \Delta \mathrm{MD}=0.05\pm 0.05\kern0.3em \left[\times 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=4e-5\right) $$ for b max = 450 s / mm 2 $$ {b}_{\mathrm{max}}=450\kern0.3em \mathrm{s}/{\mathrm{mm}}^2 $$ and Δ MD = 0 . 03 ± 0 . 03 [ × 1 0 - 3 mm 2 / s ] ( p = 4 e - 4 ) $$ \Delta \mathrm{MD}=0.03\pm 0.03\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=4e-4\right) $$ for b max = 1000 s / mm 2 $$ {b}_{\mathrm{max}}=1000\kern0.3em \mathrm{s}/{\mathrm{mm}}^2 $$ . A reduction in MD is observed by increasing the b max $$ {b}_{\mathrm{max}} $$ from 450 to 1000 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ ( Δ MD = 0 . 06 ± 0 . 04 [ × 1 0 - 3 mm 2 / s ] ( p = 1 . 6 e - 9 ) $$ \Delta \mathrm{MD}=0.06\pm 0.04\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=1.6e-9\right) $$ for M 2 $$ {M}_2 $$ and Δ MD = 0 . 08 ± 0 . 05 [ × 1 0 - 3 mm 2 / s ] ( p = 1 e - 9 ) $$ \Delta \mathrm{MD}=0.08\pm 0.05\kern0.3em \left[\times \kern0.3em 1{0}^{-3}\kern0.3em {\mathrm{mm}}^2/\mathrm{s}\right]\kern0.3em \left(p=1e-9\right) $$ for M 3 $$ {M}_3 $$ ). The difference between FA, E2A, and HA was not significant in different schemes ( p > 0 . 05 $$ p>0.05 $$ ). CONCLUSION: This work demonstrates cardiac DWI in vivo with higher b-value and higher order of motion compensated diffusion gradient waveforms than is commonly used. Increasing the motion compensation order from M 2 $$ {M}_2 $$ to M 3 $$ {M}_3 $$ and the maximum b-value from 450 to 1000 s / mm 2 $$ \mathrm{s}/{\mathrm{mm}}^2 $$ affected the MD values but FA and the angular metrics (HA and E2A) remained unchanged. Our work paves the way for cardiac DWI on the next-generation MR scanners with high-performance gradient systems.

Longitudinal effects of prenatal alcohol exposure on visual neurodevelopment over infancy.

Prenatal alcohol exposure (PAE) affects neurodevelopment in over 59 million individuals globally. Prior studies using dichotomous categorization of alcohol use and comorbid substance exposures provide limited knowledge of how prenatal alcohol specifically impacts early human neurodevelopment. In this longitudinal cohort study from Cape Town, South Africa, PAE is measured continuously-characterizing timing, dose, and drinking patterns (i.e., binge drinking). High-density electroencephalography (EEG) during a visual-evoked potential (VEP) task was collected from infants aged 8 to 52 weeks with prenatal exposure exclusively to alcohol and matched on sociodemographic factors to infants with no substance exposure in utero. First trimester alcohol exposure related to altered timing of the P1 VEP component over the first 6 months postnatally, and first trimester binge drinking exposure altered timing of the P1 VEP components such that increased exposure was associated with longer VEP latencies while increasing age was related to shorter VEP latencies (n = 108). These results suggest alcohol exposure in the first trimester may alter visual neurodevelopmental timing in early infancy. Exploratory individual-difference analysis across infants with and without PAE tested the relation between VEP latencies and myelination for a subsample of infants with usable magnetic resonance imaging (MRI) T1w and T2w scans collected at the same time point as EEG (n = 47). Decreased MRI T1w/T2w ratios (an indicator of myelin) in the primary visual cortex (n = 47) were linked to longer P1 VEP latencies. Results from these two sets of analyses suggest that prenatal alcohol and postnatal myelination may both separately impact VEP latency over infancy. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Optimisation of quantitative brain diffusion-relaxation MRI acquisition protocols with physics-informed machine learning.

Diffusion-relaxation MRI aims to extract quantitative measures that characterise microstructural tissue properties such as orientation, size, and shape, but long acquisition times are typically required. This work proposes a physics-informed learning framework to extract an optimal subset of diffusion-relaxation MRI measurements for enabling shorter acquisition times, predict non-measured signals, and estimate quantitative parameters. In vivo and synthetic brain 5D-Diffusion-T1-T2∗-weighted MRI data obtained from five healthy subjects were used for training and validation, and from a sixth participant for testing. One fully data-driven and two physics-informed machine learning methods were implemented and compared to two manual selection procedures and Cramér-Rao lower bound optimisation. The physics-informed approaches could identify measurement-subsets that yielded more consistently accurate parameter estimates in simulations than other approaches, with similar signal prediction error. Five-fold shorter protocols yielded error distributions of estimated quantitative parameters with very small effect sizes compared to estimates from the full protocol. Selected subsets commonly included a denser sampling of the shortest and longest inversion time, lowest echo time, and high b-value. The proposed framework combining machine learning and MRI physics offers a promising approach to develop shorter imaging protocols without compromising the quality of parameter estimates and signal predictions.

Neutrophilic dermatosis in a patient with an IKZF1 variant and a review of monogenic autoinflammatory disorders presenting with neutrophilic dermatoses.

Monogenic diseases of immune dysregulation should be considered in the evaluation of children presenting with recurrent neutrophilic dermatoses in association with systemic signs of inflammation, autoimmune disease, hematologic abnormalities, and opportunistic or recurrent infections. We report the case of a 2-year-old boy presenting with a neutrophilic dermatosis, found to have a novel likely pathogenic germline variant of the IKAROS Family Zinc Finger 1 (IKZF1) gene; the mutation likely results in a loss of function dimerization defective protein based on reports and studies of similar variants. IKZF1 variants could potentially lead to aberrant neutrophil chemotaxis and development of neutrophilic dermatoses. Long-term surveillance is required to monitor the development of hematologic malignancy, autoimmunity, immunodeficiency, and infection in patients with pathogenic IKZF1 germline variants.

Pore size estimation in axon-mimicking microfibers with diffusion-relaxation MRI.

PURPOSE: This study aims to evaluate two distinct approaches for fiber radius estimation using diffusion-relaxation MRI data acquired in biomimetic microfiber phantoms that mimic hollow axons. The methods considered are the spherical mean power-law approach and a T2-based pore size estimation technique. THEORY AND METHODS: A general diffusion-relaxation theoretical model for the spherical mean signal from water molecules within a distribution of cylinders with varying radii was introduced, encompassing the evaluated models as particular cases. Additionally, a new numerical approach was presented for estimating effective radii (i.e., MRI-visible mean radii) from the ground truth radii distributions, not reliant on previous theoretical approximations and adaptable to various acquisition sequences. The ground truth radii were obtained from scanning electron microscope images. RESULTS: Both methods show a linear relationship between effective radii estimated from MRI data and ground-truth radii distributions, although some discrepancies were observed. The spherical mean power-law method overestimated fiber radii. Conversely, the T2-based method exhibited higher sensitivity to smaller fiber radii, but faced limitations in accurately estimating the radius in one particular phantom, possibly because of material-specific relaxation changes. CONCLUSION: The study demonstrates the feasibility of both techniques to predict pore sizes of hollow microfibers. The T2-based technique, unlike the spherical mean power-law method, does not demand ultra-high diffusion gradients, but requires calibration with known radius distributions. This research contributes to the ongoing development and evaluation of neuroimaging techniques for fiber radius estimation, highlights the advantages and limitations of both methods, and provides datasets for reproducible research.

Macro- and micro-structural insights into primary dystonia: a UK Biobank study.

BACKGROUND: Dystonia is a hyperkinetic movement disorder with key motor network dysfunction implicated in pathophysiology. The UK Biobank encompasses > 500,000 participants, of whom 42,565 underwent brain MRI scanning. This study applied an optimized pre-processing pipeline, aimed at better accounting for artifact and improving data reliability, to assess for grey and white matter structural MRI changes between individuals diagnosed with primary dystonia and an unaffected control cohort. METHODS: Individuals with dystonia (n = 76) were identified from the UK Biobank using published algorithms, alongside an age- and sex-matched unaffected control cohort (n = 311). Grey matter morphometric and diffusion measures were assessed, together with white matter diffusion tensor and diffusion kurtosis metrics using tractography and tractometry. Post-hoc Neurite Orientation and Density Distribution Imaging (NODDI) was also undertaken for tracts in which significant differences were observed. RESULTS: Grey matter tremor-specific striatal differences were observed, with higher radial kurtosis. Tractography identified no white matter differences, however segmental tractometry identified localised differences, particularly in the superior cerebellar peduncles and anterior thalamic radiations, including higher fractional anisotropy and lower orientation distribution index in dystonia, compared to controls. Additional tremor-specific changes included lower neurite density index in the anterior thalamic radiations. CONCLUSIONS: Analysis of imaging data from one of the largest dystonia cohorts to date demonstrates microstructural differences in cerebellar and thalamic white matter connections, with architectural differences such as less orientation dispersion potentially being a component of the morphological structural changes implicated in dystonia. Distinct tremor-related imaging features are also implicated in both grey and white matter.

Maximizing SNR per unit time in diffusion MRI with multiband T-Hex spirals.

PURPOSE: The characterization of tissue microstructure using diffusion MRI (dMRI) signals is rapidly evolving, with increasing sophistication of signal representations and microstructure models. However, this progress often requires signals to be acquired with very high b-values (e.g., b > 30 ms/µm2 ), along many directions, and using multiple b-values, leading to long scan times and extremely low SNR in dMRI images. The purpose of this work is to boost the SNR efficiency of dMRI by combining three particularly efficient spatial encoding techniques and utilizing a high-performance gradient system (Gmax ≤ 300 mT/m) for efficient diffusion encoding. METHODS: Spiral readouts, multiband imaging, and sampling on tilted hexagonal grids (T-Hex) are combined and implemented on a 3T MRI system with ultra-strong gradients. Image reconstruction is performed through an iterative cg-SENSE algorithm incorporating static off-resonance distributions and field dynamics as measured with an NMR field camera. Additionally, T-Hex multiband is combined with a more conventional EPI-readout and compared with state-of-the-art blipped-CAIPIRINHA sampling. The advantage of the proposed approach is furthermore investigated for clinically available gradient performance and diffusion kurtosis imaging. RESULTS: High fidelity in vivo images with b-values up to 40 ms/µm2 are obtained. The approach provides superior SNR efficiency over other state-of-the-art multiband diffusion readout schemes. CONCLUSION: The demonstrated gains hold promise for the widespread dissemination of advanced microstructural scans, especially in clinical populations.