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There is no well-established in vivo marker of nigral degeneration in Parkinson's disease (PD). An ideal imaging marker would directly mirror the loss of substantia nigra dopaminergic neurones, which is most prominent in sub-regions called nigrosomes. High-resolution, iron-sensitive, magnetic resonance imaging (MRI) at 7T allows direct nigrosome-1 visualisation in healthy people but not in PD. Here, we investigated the feasibility of nigrosome-1 detection using 3T - susceptibility-weighted (SWI) MRI and the diagnostic accuracy that can be achieved for diagnosing PD in a clinical population. 114 high-resolution 3T - SWI-scans were reviewed consisting of a prospective case-control study in 19 subjects (10 PD, 9 controls) and a retrospective cross-sectional study in 95 consecutive patients undergoing routine clinical SWI-scans (>50 years, 9 PD, 81 non-PD, 5 non-diagnostic studies excluded). Two raters independently classified subjects into PD and non-PD according to absence or presence of nigrosome-1, followed by consensus reading. Diagnostic accuracy was assessed against clinical diagnosis as gold standard. Absolute inter- and intra-rater agreement was ≥94% (kappa≥0.82, p<0.001). In the prospective study 8/9 control and 8/10 PD; and in the retrospective study 77/81 non-PD and all 9 PD subjects were correctly classified. Diagnostic accuracy of the retrospective cohort was: sensitivity 100%, specificity 95%, NPV 1, PPV 0.69 and accuracy 96% which dropped to 91% when including non-diagnostic scans ('intent to diagnose'). The healthy nigrosome-1 can be readily depicted on high-resolution 3T - SWI giving rise to a 'swallow tail' appearance of the dorsolateral substantia nigra, and this feature is lost in PD. Visual radiological assessment yielded a high diagnostic accuracy for PD vs. an unselected clinical control population. Assessing the substantia nigra on SWI for the typical 'swallow tail' appearance has potential to become a new and easy applicable 3T MRI diagnostic tool for nigral degeneration in PD.

Response criteria for paediatric high-grade glioma vary historically and across different cooperative groups. The Response Assessment in Neuro-Oncology working group developed response criteria for adult high-grade glioma, but these were not created to meet the unique challenges in children with the disease. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address issues and unique challenges in assessing response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric high-grade glioma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric high-grade gliomas to various treatments. For areas in which scientific investigation was scarce, consensus was reached through an iterative process. RAPNO response assessment recommendations include the use of MRI of the brain and the spine, assessment of clinical status, and the use of corticosteroids or antiangiogenics. Imaging standards for brain and spine are defined. Compared with the recommendations for the management of adult high-grade glioma, for paediatrics there is inclusion of diffusion-weighted imaging and a higher reliance on T2-weighted fluid-attenuated inversion recovery. Consensus recommendations and response definitions have been established and, similar to other RAPNO recommendations, prospective validation in clinical trials is warranted.

The locus coeruleus (LC) noradrenergic system regulates arousal and modulates attention through its extensive projections across the brain. LC dysfunction has been implicated in a broad range of neurodevelopmental, neurodegenerative and psychiatric disorders, as well as in the cognitive changes observed during normal aging. Magnetic resonance imaging (MRI) has been used to characterize the human LC (elevated contrast relative to surrounding structures), but there is limited understanding of the factors underlying putative LC contrast that are critical to successful biomarker development and confidence in localizing nucleus LC. We used ultra-high-field 7T magnetic resonance imaging (MRI) to acquire T1-weighted microscopy resolution images (78μm in-plane resolution) of the LC from post-mortem tissue samples. Histological analyses were performed to characterize the distribution of tyrosine hydroxylase (TH) and neuromelanin in the scanned tissue, which allowed for direct comparison with MR microscopy images. Our results indicate that LC-MRI contrast corresponds to the location of neuromelanin cells in LC; these also correspond to norepinephrine neurons. Thus, neuromelanin appears to serve as a natural contrast agent for nucleus LC that can be used to localize nucleus LC and may have the potential to characterize neurodegenerative disease. •Elevated locus coeruleus (LC) contrast was observed in post-mortem tissue at 7T.•LC contrast was observed when neuromelanin was present in nucleus LC.•LC contrast was not observed when only tyrosine hydroxylase was present.•Neuromelanin, which accumulates with age, can be used to localize nucleus LC.

ObjectivesPatient and public involvement (PPI) was sought in the development of the protocol for the Cognitive Decline after Brain Radiosurgery (CoDe B-Rad) study, which aims to identify potential side effects of stereotactic radiosurgery (SRS). PPI served to refine the research question and methodology.DesignPPI.SettingPPI conducted online with people based in the UK. The CoDe B-Rad study is running in regional National Health Service tertiary care in the UK and is currently nearing recruitment completion.ParticipantsPatients and carers with lived experiences of brain radiotherapy. Contributors were identified through national charities.ProceduresInitial focus groups were planned, but participation proved challenging. Instead, online questionnaires, one-to-one discussions and participation in support groups were completed.ResultsAll contributors experienced changes to their cognition and/or quality of life (QoL) after radiotherapy. Quantifying the side effects of SRS and minimising them were identified as a research gap. Discussion group participation proved challenging. PPI plans were altered to accommodate the physical and mental needs of contributors. It was decided to combine the Montreal Cognitive Assessment along with European Organisation for Research and Treatment in Cancer QLQ-C30 and BN20 to capture cognitive status and QoL of patients with brain metastases and meningiomas after SRS. Patients/carers recommended for sessions to be restricted to 30 min and testing to be offered face-to-face, online, in hospital or at patients’ homes. Coproduction was not achievable with our patient population but that did not diminish the input of contributors nor the impact it had on designing the study protocol.ConclusionsIn cancer research, diligent considerations are required to ensure the suitability of involvement methods for this vulnerable population. Flexibility and adaptability of draft PPI plans are essential to achieve meaningful contributions. The protocol of the ongoing CoDe B-Rad study was positively shaped by people with lived experiences of brain radiotherapy.Trial registration numberNCT06466720 (CoDe B-Rad study).

Acute exercise suppresses appetite and alters food‐cue reactivity, but the extent exercise‐induced changes in cerebral blood flow (CBF) influences the blood‐oxygen‐level‐dependent (BOLD) signal during appetite‐related paradigms is not known. This study examined the impact of acute running on visual food‐cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five‐minute pseudo‐continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD‐fMRI was acquired during a food‐cue reactivity task before and 28 min after exercise/rest. Food‐cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤ .018). No time‐by‐trial interactions for CBF were identified (p ≥ .087). Exercise induced moderate‐to‐large reductions in subjective appetite ratings (Cohen's d = 0.53–0.84; p ≤ .024) and increased food‐cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise‐induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food‐cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF. We investigated the impact of a single running bout on cerebral blood flow (CBF) and food cue reactivity using functional magnetic resonance imaging (fMRI) in healthy men. Running did not alter the time‐course of grey matter or regional CBF up to 30 min after exercise cessation but increased food cue reactivity in brain regions implicated in attention, reward and episodic memory retrieval. Exercise‐related BOLD signal changes were detected in the presence of underlying CBF.

Despite its great potential for studying the living brain, magnetic resonance imaging (MRI) can be often limited by nuisance non-biological factors, such as hardware/software differences between scanners, which can interfere with biological variability. This lack of standardisation or harmonisation between scanners hinders reproducibility and quantifiability of MRI. Towards addressing this challenge, we present one of the most comprehensive MRI harmonisation resources, based on a travelling heads paradigm; healthy volunteers scanned repeatedly across different scanners. The Oxford-Nottingham Harmonisation (ON-Harmony) resource offers data from 20 participants each scanned on six different 3 T MRI scanners from three major vendors (GE/Philips/Siemens) across five imaging sites. Each scanning session includes five imaging modalities (T1w/T2w/dMRI/rfMRI/SWI) with protocols aligned to the UK Biobank, while for about half of the participants five within-scanner repeats are additionally acquired. The 165 multi-modal scanning sessions allow mapping of different pools of variability (biological, between-scanner, within-scanner) for hundreds of MRI-derived measures. We describe the breadth of information contained in the publicly-available data and showcase their reuse potential for evaluating efficacy of harmonisation approaches.

Background Tumour hypoxia is a recognised cause of radiotherapy treatment resistance in head and neck squamous cell carcinoma (HNSCC). Current positron emission tomography-based hypoxia imaging techniques are not routinely available in many centres. We investigated if an alternative technique called oxygen-enhanced magnetic resonance imaging (OE-MRI) could be performed in HNSCC. Methods A volumetric OE-MRI protocol for dynamic T1 relaxation time mapping was implemented on 1.5-T clinical scanners. Participants were scanned breathing room air and during high-flow oxygen administration. Oxygen-induced changes in T1 times (ΔT1) and R 2 * rates (Δ R 2 *) were measured in malignant tissue and healthy organs. Unequal variance t -test was used. Patients were surveyed on their experience of the OE-MRI protocol. Results Fifteen patients with HNSCC (median age 59 years, range 38 to 76) and 10 non-HNSCC subjects (median age 46.5 years, range 32 to 62) were scanned; the OE-MRI acquisition took less than 10 min and was well tolerated. Fifteen histologically confirmed primary tumours and 41 malignant nodal masses were identified. Median (range) of ΔT1 times and hypoxic fraction estimates for primary tumours were -3.5% (-7.0 to -0.3%) and 30.7% (6.5 to 78.6%) respectively. Radiotherapy-responsive and radiotherapy-resistant primary tumours had mean estimated hypoxic fractions of 36.8% (95% confidence interval [CI] 17.4 to 56.2%) and 59.0% (95% CI 44.6 to 73.3%), respectively ( p  = 0.111). Conclusions We present a well-tolerated implementation of dynamic, volumetric OE-MRI of the head and neck region allowing discernment of differing oxygen responses within biopsy-confirmed HNSCC. Trial registration ClinicalTrials.gov, NCT04724096 . Registered on 26 January 2021. Relevance statement MRI of tumour hypoxia in head and neck cancer using routine clinical equipment is feasible and well tolerated and allows estimates of tumour hypoxic fractions in less than ten minutes. Key points • Oxygen-enhanced MRI (OE-MRI) can estimate tumour hypoxic fractions in ten-minute scanning. • OE-MRI may be incorporable into routine clinical tumour imaging. • OE-MRI has the potential to predict outcomes after radiotherapy treatment. Graphical Abstract

This study concerns glulisine, a rapid-acting insulin analogue that plays a fundamental role in diabetes management. We have applied a combination of methods namely X-ray crystallography, and biophysical characterisation to provide a detailed insight into the structure and function of glulisine. X-ray data provided structural information to a resolution of 1.26 Å. Crystals belonged to the H3 space group with hexagonal (centred trigonal) cell dimensions a = b = 82.44 and c = 33.65 Å with two molecules in the asymmetric unit. A unique position of D21Glu, not present in other fast-acting analogues, pointing inwards rather than to the outside surface was observed. This reduces interactions with neighbouring molecules thereby increasing preference of the dimer form. Sedimentation velocity/equilibrium studies revealed a trinary system of dimers and hexamers/dihexamers in dynamic equilibrium. This new information may lead to better understanding of the pharmacokinetic and pharmacodynamic behaviour of glulisine which might aid in improving formulation regarding its fast-acting role and reducing side effects of this drug.

The structure and function of clinical dosage insulin and its analogues were assessed. This included 'native insulins' (human recombinant, bovine, porcine), 'fast-acting analogues' (aspart, glulisine, lispro) and 'slow-acting analogues' (glargine, detemir, degludec). Analytical ultracentrifugation, both sedimentation velocity and equilibrium experiments, were employed to yield distributions of both molar mass and sedimentation coefficient of all nine insulins. Size exclusion chromatography, coupled to multi-angle light scattering, was also used to explore the function of these analogues. On ultracentrifugation analysis, the insulins under investigation were found to be in numerous conformational states, however the majority of insulins were present in a primarily hexameric conformation. This was true for all native insulins and two fast-acting analogues. However, glargine was present as a dimer, detemir was a multi-hexameric system, degludec was a dodecamer (di-hexamer) and glulisine was present as a dimer-hexamer-dihexamer system. However, size-exclusion chromatography showed that the two hexameric fast-acting analogues (aspart and lispro) dissociated into monomers and dimers due to the lack of zinc in the mobile phase. This comprehensive study is the first time all nine insulins have been characterised in this way, the first time that insulin detemir have been studied using analytical ultracentrifugation and the first time that insulins aspart and glulisine have been studied using sedimentation equilibrium. The structure and function of these clinically administered insulins is of critical importance and this research adds novel data to an otherwise complex functional physiological protein.

DICOM is an industry-standard for medical imaging data targeted at interoperability across systems. This enables transfer, storage and processing of imaging data regardless of the manufacturer. Pragmatically, manufacturers often store detailed acquisition parameters in private rather than public DICOM tags. In parallel, the DICOM standard itself has gradually evolved by introducing new public tags and properties to better capture emerging imaging technologies. Accurately extracting these details is essential for reproducible neuroimaging research. To address this need, we created a series of DICOM datasets illustrating how various manufacturers encode acquisition details that are critical for modern processing and analysis. These minimal test cases, covering CT and MR modalities, highlight manufacturer-specific conventions, including the use of public tags, private tags, and proprietary data structures. For each DICOM dataset, we provide corresponding NIfTI-formatted images with metadata JSON files following the BIDS standard, using consistent terminology to mitigate variations in how manufacturers encode acquisition details. Our repository provides validation datasets for any tool that is intended to extract acquisition details from medical imaging data.