Recommendations for quantitative cerebral perfusion MRI using multi-timepoint arterial spin labeling: Acquisition, quantification, and clinical applications.

Accurate assessment of cerebral perfusion is vital for understanding the hemodynamic processes involved in various neurological disorders and guiding clinical decision-making. This guidelines article provides a comprehensive overview of quantitative perfusion imaging of the brain using multi-timepoint arterial spin labeling (ASL), along with recommendations for its acquisition and quantification. A major benefit of acquiring ASL data with multiple label durations and/or post-labeling delays (PLDs) is being able to account for the effect of variable arterial transit time (ATT) on quantitative perfusion values and additionally visualize the spatial pattern of ATT itself, providing valuable clinical insights. Although multi-timepoint data can be acquired in the same scan time as single-PLD data with comparable perfusion measurement precision, its acquisition and postprocessing presents challenges beyond single-PLD ASL, impeding widespread adoption. Building upon the 2015 ASL consensus article, this work highlights the protocol distinctions specific to multi-timepoint ASL and provides robust recommendations for acquiring high-quality data. Additionally, we propose an extended quantification model based on the 2015 consensus model and discuss relevant postprocessing options to enhance the analysis of multi-timepoint ASL data. Furthermore, we review the potential clinical applications where multi-timepoint ASL is expected to offer significant benefits. This article is part of a series published by the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group, aiming to guide and inspire the advancement and utilization of ASL beyond the scope of the 2015 consensus article.

AlphaKnot: server to analyze entanglement in structures predicted by AlphaFold methods.

AlphaKnot is a server that measures entanglement in AlphaFold-solved protein models while considering pLDDT confidence values. AlphaKnot has two main functions: (i) providing researchers with a webserver for analyzing knotting in their own AlphaFold predictions and (ii) providing a database of knotting in AlphaFold predictions from the 21 proteomes for which models have been published prior to 2022. The knotting is defined in a probabilistic fashion. The knotting complexity of proteins is presented in the form of a matrix diagram which shows users the knot type for the entire polypeptide chain and for each of its subchains. The dominant knot types as well as the computed locations of the knot cores (i.e. minimal portions of protein backbones that form a given knot type) are shown for each protein structure. Based mainly on the pLDDT confidence values, entanglements are classified as Knots, Unsure, and Artifacts. The database portion of the server can be used, for example, to examine protein geometry and entanglement-function correlations, as a reference set for protein modeling, and for facilitating evolutional studies. The AlphaKnot server can be found at https://alphaknot.cent.uw.edu.pl/.

The unintended consequences of artificial intelligence in paediatric radiology.

Over the past decade, there has been a dramatic rise in the interest relating to the application of artificial intelligence (AI) in radiology. Originally only 'narrow' AI tasks were possible; however, with increasing availability of data, teamed with ease of access to powerful computer processing capabilities, we are becoming more able to generate complex and nuanced prediction models and elaborate solutions for healthcare. Nevertheless, these AI models are not without their failings, and sometimes the intended use for these solutions may not lead to predictable impacts for patients, society or those working within the healthcare profession. In this article, we provide an overview of the latest opinions regarding AI ethics, bias, limitations, challenges and considerations that we should all contemplate in this exciting and expanding field, with a special attention to how this applies to the unique aspects of a paediatric population. By embracing AI technology and fostering a multidisciplinary approach, it is hoped that we can harness the power AI brings whilst minimising harm and ensuring a beneficial impact on radiology practice.

Current state and guidance on arterial spin labeling perfusion MRI in clinical neuroimaging.

This article focuses on clinical applications of arterial spin labeling (ASL) and is part of a wider effort from the International Society for Magnetic Resonance in Medicine (ISMRM) Perfusion Study Group to update and expand on the recommendations provided in the 2015 ASL consensus paper. Although the 2015 consensus paper provided general guidelines for clinical applications of ASL MRI, there was a lack of guidance on disease-specific parameters. Since that time, the clinical availability and clinical demand for ASL MRI has increased. This position paper provides guidance on using ASL in specific clinical scenarios, including acute ischemic stroke and steno-occlusive disease, arteriovenous malformations and fistulas, brain tumors, neurodegenerative disease, seizures/epilepsy, and pediatric neuroradiology applications, focusing on disease-specific considerations for sequence optimization and interpretation. We present several neuroradiological applications in which ASL provides unique information essential for making the diagnosis. This guidance is intended for anyone interested in using ASL in a routine clinical setting (i.e., on a single-subject basis rather than in cohort studies) building on the previous ASL consensus review.

Intramuscular aponeuroses and fiber bundle morphology of the five bellies of flexor digitorum superficialis: A three-dimensional modeling study.

Restoring balanced function of the five bellies of flexor digitorum superficialis (FDS) following injury requires knowledge of the muscle architecture and the arrangement of the contractile and connective tissue elements. No three-dimensional (3D) studies of FDS architecture were found in the literature. The purpose was to (1) digitize/model in 3D the contractile/connective tissue elements of FDS, (2) quantify/compare architectural parameters of the bellies and (3) assess functional implications. The fiber bundles (FBs)/aponeuroses of the bellies of FDS were dissected and digitized (MicroScribe® Digitizer) in 10 embalmed specimens. Data were used to construct 3D models of FDS to determine/compare the morphology of each digital belly and quantify architectural parameters to assess functional implications. FDS consists of five morphologically and architecturally distinct bellies, a proximal belly, and four digital bellies. FBs of each belly have unique attachment sites to one or more of the three aponeuroses (proximal/distal/median). The proximal belly is connected through the median aponeurosis to the bellies of the second and fifth digits. The third belly exhibited the longest mean FB length (72.84 ± 16.26 mm) and the proximal belly the shortest (30.49 ± 6.45 mm). The third belly also had the greatest mean physiological cross-sectional area, followed by proximal/second/fourth/fifth. Each belly was found to have distinct excursion and force-generating capabilities based on their 3D morphology and architectural parameters. Results of this study provide the basis for the development of in vivo ultrasound protocols to study activation patterns of FDS during functional activities in normal and pathologic states.

Amino acid variants of SARS-CoV-2 papain-like protease have impact on drug binding.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused both a health and economic crisis around the world. Its papain-like protease (PLpro) is one of the protein targets utilized in designing new drugs that would aid vaccines in the fight against the virus. Although there are already several potential candidates for a good inhibitor of this protein, the degree of variability of the protein itself is not taken into account. As an RNA virus, SARS-CoV-2 can mutate to a high degree, but PLpro variability has not been studied to date. Based on sequence data available in databases, we analyzed the mutational potential of this protein. We focused on the effect of observed mutations on inhibitors' binding mode and their efficacy as well as protein's activity. Our analysis identifies five mutations that should be monitored and included in the drug design process: P247S, E263D-Y264H and T265A-Y268C.

Arterial Spin Labeling Applications in Pediatric and Adult Neurologic Disorders.

Arterial spin labeling (ASL) is a powerful noncontrast magnetic resonance imaging (MRI) technique that enables quantitative evaluation of brain perfusion. To optimize the clinical and research utilization of ASL, radiologists and physicists must understand the technical considerations and age-related variations in normal and disease states. We discuss advanced applications of ASL across the lifespan, with example cases from children and adults covering a wide variety of pathologies. Through literature review and illustrated clinical cases, we highlight the subtleties as well as pitfalls of ASL interpretation. First, we review basic physical principles, techniques, and artifacts. This is followed by a discussion of normal perfusion variants based on age and physiology. The three major categories of perfusion abnormalities-hypoperfusion, hyperperfusion, and mixed patterns-are covered with an emphasis on clinical interpretation and relationship to the disease process. Major etiologies of hypoperfusion include large artery, small artery, and venous disease; other vascular conditions; global hypoxic-ischemic injury; and neurodegeneration. Hyperperfusion is characteristic of vascular malformations and tumors. Mixed perfusion patterns can be seen with epilepsy, migraine, trauma, infection/inflammation, and toxic-metabolic encephalopathy. LEVEL OF EVIDENCE: 4 TECHNICAL EFFICACY STAGE: 3.

PTEN somatic mutations contribute to spectrum of cerebral overgrowth.

Phosphatase and tensin homologue (PTEN) regulates cell growth and survival through inhibition of the mammalian target of rapamycin (MTOR) signalling pathway. Germline genetic variation of PTEN is associated with autism, macrocephaly and PTEN hamartoma tumour syndromes. The effect of developmental PTEN somatic mutations on nervous system phenotypes is not well understood, although brain somatic mosaicism of MTOR pathway genes is an emerging cause of cortical dysplasia and epilepsy in the paediatric population. Here we report two somatic variants of PTEN affecting a single patient presenting with intractable epilepsy and hemimegalencephaly that varied in clinical severity throughout the left cerebral hemisphere. High-throughput sequencing analysis of affected brain tissue identified two somatic variants in PTEN. The first variant was present in multiple cell lineages throughout the entire hemisphere and associated with mild cerebral overgrowth. The second variant was restricted to posterior brain regions and affected the opposite PTEN allele, resulting in a segmental region of more severe malformation, and the only neurons in which it was found by single-nuclei RNA-sequencing had a unique disease-related expression profile. This study reveals brain mosaicism of PTEN as a disease mechanism of hemimegalencephaly and furthermore demonstrates the varying effects of single- or bi-allelic disruption of PTEN on cortical phenotypes.

Guidelines for magnetic resonance imaging in pediatric head and neck pathologies: a multicentre international consensus paper.

The use of standardized imaging protocols is paramount in order to facilitate comparable, reproducible images and, consequently, to optimize patient care. Standardized MR protocols are lacking when studying head and neck pathologies in the pediatric population. We propose an international, multicenter consensus paper focused on providing the best combination of acquisition time/technical requirements and image quality. Distinct protocols for different regions of the head and neck and, in some cases, for specific pathologies or clinical indications are recommended. This white paper is endorsed by several international scientific societies and it is the result of discussion, in consensus, among experts in pediatric head and neck imaging.

The moderating role of gender in the association between quality of social relationships and sleep.

To determine whether the association between perceived social support or strain in close relationships and sleep outcomes varies by gender. Participants were selected from the Biomarker projects of either the MIDUS II or MIDUS Refresher study if they were in a married-or married-like relationship and shared a bed with their partner (N = 989). A subsample also participated in a seven-day sleep study (n = 282). Perceived social support and strain from partner, family, and friends were examined by self-report questionnaires. We used the Pittsburgh Sleep Quality Index, sleep daily diary, and actigraphy to measure both subjective and objective sleep. Social support and strain were both associated with sleep outcomes. Specifically, higher social support was associated with fewer daily reports of light sleep and feeling more rested in the morning, while higher social strain was associated with higher clinical sleep disturbance. For women, but not men, social support was significantly associated with lower daily sleep disturbance while perceived social strain was significantly associated with higher daily sleep disturbance, lighter sleep, feeling less rested in the morning, lower sleep efficiency, and longer sleep onset latency. Mainly among women, social support and strain are associated with an important transdiagnostic health outcome-sleep-which may have implications for a wide range of health disparities. Interpersonal stressors may increase health risks differently for women compared to men and one mechanism that may link social relationships to long-term health outcomes is sleep.

KRIT1-positive hyperkeratotic cutaneous capillary venous malformation.

Cerebral cavernous malformations (CCM) may present in sporadic or familial forms, with different cutaneous manifestations including deep blue nodules, capillary malformations, and hyperkeratotic cutaneous capillary venous malformations (HCCVM). We report the case of an infant with a KRIT1-positive HCCVM associated with familial CCM. Moreover, histopathology showed positive immunohistochemical stain with GLUT1, further expanding the differential diagnosis of GLUT1-positive vascular anomalies.

Utilization of neonatal sedation and anesthesia: an SPR survey.

BACKGROUND: There is little data regarding the use of sedation and anesthesia for neonatal imaging, with practice patterns varying widely across institutions. OBJECTIVE: To understand the current utilization of sedation and anesthesia for neonatal imaging, and review the current literature and recommendations. MATERIALS AND METHODS: One thousand, two hundred twenty-six questionnaire invitations were emailed to North American physician members of the Society for Pediatric Radiology using the Survey Monkey platform. Descriptive statistical analysis of the responses was performed. RESULTS: The final results represented 59 institutions from 26 U.S. states, the District of Columbia and three Canadian provinces. Discrepant responses from institutions with multiple respondents (13 out of 59 institutions) were prevalent in multiple categories. Of the 80 total respondents, slightly more than half (56%) were associated with children's hospitals and 44% with the pediatric division of an adult radiology department. Most radiologists (70%) were cognizant of the neonatal sedation policies in their departments. A majority (89%) acknowledged awareness of neurotoxicity concerns in the literature and agreed with the validity of these concerns. In neonates undergoing magnetic resonance imaging (MRI), 46% of respondents reported attempting feed and bundle in all patients and an additional 46% attempt on a case-by-case basis, with most (35%) using a single swaddling attempt before sedation. Sedation was most often used for neonatal interventional procedures (93%) followed by MR (85%), nuclear medicine (48%) and computed tomography (31%). More than half of respondents (63%) reported an average success rate of greater than 50% when using neonatal sedation for MR. CONCLUSION: Current practice patterns, policies and understanding of the use of sedation and anesthesia for neonatal imaging vary widely across institutions in North America, and even among radiologists from the same institution. Our survey highlights the need for improved awareness, education, and standardization at both the institutional level and the societal level. Awareness of the potential for anesthetic neurotoxicity and success of non-pharmacologic approaches to neonatal imaging is crucial, along with education of health care personnel, systematic approaches to quality control and improvement, and integration of evidence-based protocols into clinical practice.

Longitudinal MRI brain volume changes over one year in children with mucopolysaccharidosis types IIIA and IIIB.

OBJECTIVE: To quantify changes in segmented brain volumes over 12 months in children with mucopolysaccharidosis types IIIA and IIIB (MPS IIIA and IIIB). METHODS: In order to establish suitable outcome measures for clinical trials, twenty-five children greater than 2 years of age were enrolled in a prospective natural history study of MPS IIIA and IIIB at Nationwide Children's Hospital. Data from sedated non-contrast brain 3 T MRIs and neuropsychological measures were reviewed from the baseline visit and at 12-month follow-up. No intervention beyond standard clinical care was provided. Age- and sex-matched controls were gathered from the National Institute of Mental Health Data Archive. Automated brain volume segmentation with longitudinal processing was performed using FreeSurfer. RESULTS: Of the 25 subjects enrolled with MPS III, 17 children (4 females, 13 males) completed at least one MRI with interpretable volumetric data. The ages ranged from 2.8 to 13.7 years old (average 7.2 years old) at enrollment, including 8 with MPS IIIA and 9 with MPS IIIB. At baseline, individuals with MPS III demonstrated reduced cerebral white matter and corpus callosum volumes, but greater volumes of the lateral ventricles, cerebellar cortex, and cerebellar white matter compared to controls. Among the 13 individuals with MPS III with two interpretable MRIs, there were annualized losses or plateaus in supratentorial brain tissue volumes (cerebral cortex -42.10 ± 18.52 cm3/year [mean ± SD], cerebral white matter -4.37 ± 11.82 cm3/year, subcortical gray matter -6.54 ± 3.63 cm3/year, corpus callosum -0.18 ± 0.62 cm3/yr) and in cerebellar cortex (-0.49 ± 12.57 cm3/year), with a compensatory increase in lateral ventricular volume (7.17 ± 6.79 cm3/year). Reductions in the cerebral cortex and subcortical gray matter were more striking in individuals younger than 8 years of age. Greater cerebral cortex volume was associated with higher fine and gross motor functioning on the Mullen Scales of Early Learning, while greater subcortical gray matter volume was associated with higher nonverbal functioning on the Leiter International Performance Scale. Larger cerebellar cortex was associated with higher receptive language performance on the Mullen, but greater cerebellar white matter correlated with worse adaptive functioning on the Vineland Adaptive Behavioral Scales and visual problem-solving on the Mullen. CONCLUSIONS: Loss or plateauing of supratentorial brain tissue volumes may serve as longitudinal biomarkers of MPS III age-related disease progression compared to age-related growth in typically developing controls. Abnormally increased cerebellar white matter in MPS III, and its association with worse performance on neuropsychological measures, suggest the possibility of pathophysiological mechanisms distinct from neurodegeneration-associated atrophy that warrant further investigation.

Higher temporal resolution multiband fMRI provides improved presurgical language maps.

PURPOSE: We investigated the hypothesis that increasing fMRI temporal resolution using a multiband (MB) gradient echo-echo planar imaging (GRE-EPI) pulse sequence provides fMRI language maps of higher statistical quality than those acquired with a traditional GRE-EPI sequence. METHODS: This prospective study enrolled 29 consecutive patients receiving language fMRI prior to a potential brain resection for tumor, AVM, or epilepsy. A 4-min rhyming task was performed at 3.0 Tesla with a traditional GRE-EPI pulse sequence (TR = 2000, TE = 30, matrix = 64/100%, slice = 4/0, FOV = 24, slices = 30, time points = 120) and an additional MB GRE-EPI pulse sequence with an acceleration factor of 6 (TR = 333, TE = 30, matrix 64/100%, slice = 4/0, FOV = 24, time points = 720). Spatially filtered t statistical maps were generated. Volumes of interest (VOIs) were drawn around activations at Broca's, dorsolateral prefrontal cortex, Wernicke's, and the visual word form areas. The t value maxima were measured for the overall brain and each of the VOIs. A paired t test was performed for the corresponding traditional and MB GRE-EPI measurements. RESULTS: The mean age of subjects was 42.6 years old (18-75). Sixty-two percent were male. The average overall brain t statistic maxima for the MB pulse sequence (t = 15.4) was higher than for the traditional pulse sequence (t = 9.3, p = < .0001). This also held true for Broca's area (p < 0.0001), Wernicke's area (p < .0001), dorsolateral prefrontal cortex (p < .0001), and the visual word form area (p < .0001). CONCLUSION: A MB GRE-EPI fMRI pulse sequence employing high temporal resolution provides clinical fMRI language maps of greater statistical significance than those obtained with a traditional GRE-EPI sequence.

Abnormal Vestibular-Ocular Reflexes in Children With Cortical Visual Impairment.

BACKGROUND: To determine whether the vestibular-ocular reflexes (VORs) can be affected by central nervous system injury in children with cortical visual impairment (CVI). METHODS: Retrospective case series. Twenty consecutive children with CVI who presented to a pediatric ophthalmology practice over an 18-month period were included in the study. Horizontal and vertical VORs were assessed by a pediatric neuro-ophthalmologist using the standard doll's head maneuver. MRI studies were independently reviewed by a pediatric neuroradiologist in a masked fashion. The main outcome measures were the integrity of the VORs and the presence of brainstem abnormalities on MRI. RESULTS: VORs were found to be absent or severely impaired in 13/20 (65%) children with CVI. More surprisingly, the doll's head maneuver failed to substantially overcome the deviated eye position in 8/13 (62%) children with conjugate gaze deviations. Reduced brainstem size and signal abnormalities were found in 4/7 children with normal VORs and in 9/13 children with abnormal VORs (P = 0.6), showing noncorrelation with the integrity of the VOR. CONCLUSION: VORs are commonly impaired in children with CVI. This ocular motor deficit reflects the diffuse cortical and subcortical injury that often accompanies perinatal injury to the developing brain. Consequently, these children may lack important visual compensatory mechanisms to stabilize gaze during head movements. This knowledge can help in planning visual rehabilitation.

Components of a magnetic resonance imaging system and their relationship to safety and image quality.

Magnetic resonance imaging (MRI) is a powerful diagnostic tool that can be optimized to display a wide range of clinical conditions. An MRI system consists of four major components: a main magnet formed by superconducting coils, gradient coils, radiofrequency (RF) coils, and computer systems. Each component has safety considerations. Unless carefully controlled, the MRI machine's strong static magnetic field could turn a ferromagnetic object into a harmful projectile or cause vertigo and headache. Switching magnetic fields in the gradients evokes loud noises in the scanner, which can be mitigated by ear protection. Gradients also generate varying magnetic fields that can cause peripheral nerve stimulation and muscle twitching. Magnetic fields produced by RF coils deposit energy in the body and can cause tissue heating (with the potential to cause skin burns). In this review, we provide an overview of the components of a typical clinical MRI scanner and its associated safety issues. We also discuss how the relationship between the scanning parameters can be manipulated to improve image quality while ensuring a safe operational environment for the patients and staff. Understanding the strengths and limitations of these parameters can enable users to choose optimal techniques for image acquisition, apply them in clinical practice, and improve the diagnostic accuracy of an MRI examination.

Ultrasound of congenital spine anomalies.

Ultrasonography (US) is the first-line imaging modality for screening neonates and young infants with suspected spinal abnormalities. Whether performed for a suspicious congenital skin lesion, such as a lumbosacral tract or lipomatous mass, or abnormal neurological findings, US can help define spinal anatomy, characterize congenital spine malformations, and direct further work-up and management. The purpose of this article is to review the diagnostic imaging approach to infant spine US, including technique and indications, normal anatomy and variants with a focus on embryological origins, and classification and diagnosis of congenital spine malformations.

Magnetic resonance imaging quality control, quality assurance and quality improvement.

Quality in MR imaging is a comprehensive process that encompasses scanner performance, clinical processes for efficient scanning and reporting, as well as data-driven improvement involving measurement of key performance indicators. In this paper, the authors review this entire process. This article provides a framework for establishing a successful MR quality program. The collective experiences of the authors across a spectrum of pediatric hospitals is summarized here.

Evaluation of Technical Feasibility of Reusing Coal Ash in Dense Asphalt Mixes by Assessing Mechanical Performance.

This manuscript evaluates the technical feasibility of reusing coal ash in the formulation design of dense asphalt mixes. Physicochemical and mineralogical properties of fly and bottom ash matrixes prepared with coal ash were analyzed by scanning electron microscopy (SEM), X-Ray diffraction (XRD), semi-quantitative spectrometry by X-Ray fluorescence (XRF) and surface characterization by Nitrogen (N2) adsorption. Filler fractions under 0.075 mm with 6.0% in weight from an entirely gneissic aggregate gradation curve taken as reference were compared to identical mixes prepared with fly and bottom ashes individually and also to a combined sample with 3.0% of each ash type. Tests on compaction ability with gyratory shear press, resistance to action of water and to rutting were carried out to compare mechanical performance. The results indicate that both gneissic and coal ash fillers do not form dipoles of effective electric attractions to bituminous matrixes, resulting in inert and hydrophilic behavior regarding to action of water, respectively. Despite surface and morphologic characteristics underlying the mechanical performance of gneissic fillers, coal ash matrixes have shown, in general, good technical feasibility to be used in asphalt mixes.

SARS-CoV-2 Papain-Like Protease Potential Inhibitors-In Silico Quantitative Assessment.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) encodes the papain-like protease (PLpro). The protein not only plays an essential role in viral replication but also cleaves ubiquitin and ubiquitin-like interferon-stimulated gene 15 protein (ISG15) from host proteins, making it an important target for developing new antiviral drugs. In this study, we searched for novel, noncovalent potential PLpro inhibitors by employing a multistep in silico screening of a 15 million compound library. The selectivity of the best-scored compounds was evaluated by checking their binding affinity to the human ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), which, as a deubiquitylating enzyme, exhibits structural and functional similarities to the PLpro. As a result, we identified 387 potential, selective PLpro inhibitors, from which we retrieved the 20 best compounds according to their IC50 values toward PLpro estimated by a multiple linear regression model. The selected candidates display potential activity against the protein with IC50 values in the nanomolar range from approximately 159 to 505 nM and mostly adopt a similar binding mode to the known, noncovalent SARS-CoV-2 PLpro inhibitors. We further propose the six most promising compounds for future in vitro evaluation. The results for the top potential PLpro inhibitors are deposited in the database prepared to facilitate research on anti-SARS-CoV-2 drugs.