Detection of Metabolites by Proton Ex Vivo NMR, in Vivo MR Spectroscopy Peaks and Tissue Content Analysis: Biochemical-Magnetic Resonance Correlation: Preliminary Results

*Aim*: Metabolite concentrations by in vivo magnetic resonance spectroscopy and ex vivo NMR spectroscopy were compared with excised normal human tissue relaxation times and tissue homogenate contents.

*Hypothesis*: Biochemical analysis combined with NMR and MR spectroscopy defines better tissue analysis.

*Materials and Methods*: Metabolites were measured using peak area, amplitude and molecular weights of metabolites in the reference solutions. In normal brain and heart autopsy, muscle and liver biopsy tissue ex vivo NMR peaks and spin-lattice (T1) and spin-spin (T2) relaxation times, were compared with diseased tissue NMR data in meningioma brain, myocardial infarct heart, duchene-muscular-dystrophy muscle and diffused-liver-injury liver after respective in vivo proton MR spectroscopy was done. NMR data was compared with tissue homogenate contents and serum levels of biochemical parameters.

*Results*: The quantitation of smaller NMR visible metabolites was feasible for both ex vivo NMR and in vivo MR spectroscopy. Ex vivo H-1 NMR and in vivo MRS metabolite characteristic peaks (disease/normal data represented as fold change), T1 and T2, and metabolites in tissue homogenate and serum indicated muscle fibrosis in DMD, cardiac energy depletion in MI heart, neuronal dysfunction in meningioma brain and carbohydrate-lipid metabolic crisis in DLI liver tissues.

*Conclusion*: This preliminary report highlights the biochemical-magnetic resonance correlation as basis of magnetic resonance spectroscopic imaging data interpretation of disease

Joint Total Variation ESTATICS for Robust Multi-Parameter Mapping

Quantitative magnetic resonance imaging (qMRI) derives tissue-specific parameters -- such as the apparent transverse relaxation rate R2*, the longitudinal relaxation rate R1 and the magnetisation transfer saturation -- that can be compared across sites and scanners and carry important information about the underlying microstructure. The multi-parameter mapping (MPM) protocol takes advantage of multi-echo acquisitions with variable flip angles to extract these parameters in a clinically acceptable scan time. In this context, ESTATICS performs a joint loglinear fit of multiple echo series to extract R2* and multiple extrapolated intercepts, thereby improving robustness to motion and decreasing the variance of the estimators. In this paper, we extend this model in two ways: (1) by introducing a joint total variation (JTV) prior on the intercepts and decay, and (2) by deriving a nonlinear maximum \emph{a posteriori} estimate. We evaluated the proposed algorithm by predicting left-out echoes in a rich single-subject dataset. In this validation, we outperformed other state-of-the-art methods and additionally showed that the proposed approach greatly reduces the variance of the estimated maps, without introducing bias.Comment: 11 pages, 2 figures, 1 table, conference paper, accepted at MICCAI 202

The prognostic value of magnetic resonance imaging in moderate and severe traumatic brain injury : a Systematic Review and Meta-Analysis

Les traumatismes craniocérébraux constituent une cause importante de mortalité et de morbidité à travers le monde, et représentent un fardeau socioéconomique important dans les pays développés en raison de l'incapacité résiduelle post-traumatique dont souffrent les patients après leur traumatisme. Malgré la fréquence élevée d'issues cliniques défavorables à long terme, il existe actuellement peu d'indicateurs pronostiques permettant de guider le clinicien dans la prise en charge aiguë de ces patients et de conseiller leurs familles et proches. Plus de quatre décennies d'études observationnelles ont examiné l'utilisation de l'imagerie par résonance magnétique effectuée en phase aiguë dans son rôle potentiel à distinguer rapidement l'issue clinique post-traumatisme à long terme chez ces patients. Le présent travail vise donc à déterminer la valeur pronostique de l'imagerie par résonance magnétique effectuée en phase aiguë de traitement suite à un traumatisme craniocérébral modéré ou grave chez l'adulte, en utilisant une méthodologie de revue systématique et méta-analyse pronostique, afin d'identifier toutes les études évaluant la relation entre les modèles de lésions identifiés par résonance magnétique et l'issue clinique à long terme. Nos travaux ont identifié 58 études individuelles. Après méta-analyse, les lésions localisées dans le tronc cérébral se sont révélées être associées à une mortalité augmentée (toutes causes confondues) et une issue neurologique défavorable alors que les lésions compatibles avec une lésion axonale diffuse ont été associées à une augmentation du risque d'issue neurologique défavorable. Deux échelles de classement basées sur la gravité de la lésion ont été associées à des issues neurologiques de plus en plus défavorables au fur et à mesure de l'augmentation du nombre de structures cérébrales caudales touchées, confirmant ainsi l'importance des lésions profondes. Ces résultats démontrent l'utilité pronostique de l'imagerie par résonance magnétique effectuée rapidement après un traumatisme craniocérébral et indiquent la nécessité d'entreprendre des études pronostiques de cohorte de haute qualité et bien contrôlées, en raison du risque élevé de biais dans la littérature actuelle.Traumatic brain injury is a major cause of mortality and morbidity worldwide and represents a significant socioeconomic burden in developed nations due to residual post-trauma disability among survivors. Despite high rates of long-term unfavourable outcome, few prognostic indicators currently exist to guide early clinical management and counsel family and friends of patients. Over four decades of observational studies have examined the potential role of early magnetic resonance imaging of the brain to distinguish long-term clinical outcome by examining lesion patterns identifiable soon after trauma. This present work thus aims to determine the prognostic value of early magnetic resonance imaging following moderate or severe traumatic brain injury in adults by employing prognostic systematic review and meta-analysis methodology to identify all published studies assessing the relationship between magnetic resonance lesion patterns and long-term clinical outcome. Our search identified 58 individual studies; following meta-analysis, lesions located in the brainstem were associated with all-cause mortality and unfavourable neurological outcome while shear injury patterns compatible with diffuse axonal injury anywhere in the brain were associated with increased risk of unfavourable neurological outcome. Two scoring systems based on lesion depth were associated with progressively worse neurological outcomes as more caudal cerebral structures were affected, confirming the importance of deep lesions. These findings demonstrate the prognostic utility of magnetic resonance imaging early following traumatic brain injury and indicate the need for high quality, well-controlled, prognostic cohort studies given the elevated risk of bias in the current body of literature

MAGNIMS recommendations for harmonization of MRI data in MS multicenter studies

Harmonization; MRI; Multiple sclerosisHarmonització; Ressonància magnètica; Esclerosi múltipleArmonización; Resonancia magnética; Esclerosis múltipleThere is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. However, differences in MRI acquisition parameters, image analysis and data storage across sites, with their potential bias, represent a substantial constraint. This review focuses on the state of the art, recent technical advances, and desirable future developments of the harmonization of acquisition, analysis and storage of large-scale multicentre MRI data of MS cohorts. Huge efforts are currently being made to achieve all the requirements needed to provide harmonized MRI datasets in the MS field, as proper management of large imaging datasets is one of our greatest opportunities and challenges in the coming years. Recommendations based on these achievements will be provided here. Despite the advances that have been made, the complexity of these tasks requires further research by specialized academical centres, with dedicated technical and human resources. Such collective efforts involving different professional figures are of crucial importance to offer to MS patients a personalised management while minimizing consumption of resources

European Ultrahigh-Field Imaging Network for Neurodegenerative Diseases (EUFIND).

INTRODUCTION: The goal of European Ultrahigh-Field Imaging Network in Neurodegenerative Diseases (EUFIND) is to identify opportunities and challenges of 7 Tesla (7T) MRI for clinical and research applications in neurodegeneration. EUFIND comprises 22 European and one US site, including over 50 MRI and dementia experts as well as neuroscientists. METHODS: EUFIND combined consensus workshops and data sharing for multisite analysis, focusing on 7 core topics: clinical applications/clinical research, highest resolution anatomy, functional imaging, vascular systems/vascular pathology, iron mapping and neuropathology detection, spectroscopy, and quality assurance. Across these topics, EUFIND considered standard operating procedures, safety, and multivendor harmonization. RESULTS: The clinical and research opportunities and challenges of 7T MRI in each subtopic are set out as a roadmap. Specific MRI sequences for each subtopic were implemented in a pilot study presented in this report. Results show that a large multisite 7T imaging network with highly advanced and harmonized imaging sequences is feasible and may enable future multicentre ultrahigh-field MRI studies and clinical trials. DISCUSSION: The EUFIND network can be a major driver for advancing clinical neuroimaging research using 7T and for identifying use-cases for clinical applications in neurodegeneration

MAGNIMS recommendations for harmonization of MRI data in MS multicenter studies

There is an increasing need of sharing harmonized data from large, cooperative studies as this is essential to develop new diagnostic and prognostic biomarkers. In the field of multiple sclerosis (MS), the issue has become of paramount importance due to the need to translate into the clinical setting some of the most recent MRI achievements. However, differences in MRI acquisition parameters, image analysis and data storage across sites, with their potential bias, represent a substantial constraint. This review focuses on the state of the art, recent technical advances, and desirable future developments of the harmonization of acquisition, analysis and storage of large-scale multicentre MRI data of MS cohorts. Huge efforts are currently being made to achieve all the requirements needed to provide harmonized MRI datasets in the MS field, as proper management of large imaging datasets is one of our greatest opportunities and challenges in the coming years. Recommendations based on these achievements will be provided here. Despite the advances that have been made, the complexity of these tasks requires further research by specialized academical centres, with dedicated technical and human resources. Such collective efforts involving different professional figures are of crucial importance to offer to MS patients a personalised management while minimizing consumption of resource

Demographic, multi-morbidity and genetic impact on myocardial involvement and its recovery from COVID-19 : protocol design of COVID-HEART-a UK, multicentre, observational study

Acknowledgements CB acknowledges British Heart Foundation support (RE/18/6134217). GPM is funded by a NIHR Research Professorship (RP‐2017‐08‐ST2‐007). CM is funded by a NIHR Clinician Scientist Award (CS‐2015‐15‐003). VMF and SN acknowledge the NIHR Oxford BRC for support of this study. CBD is in part supported by the NIHR Biomedical Research Centre at University Hospitals Bristol NHS Foundation Trust and the University of Bristol. Additional support was provided by the NIHR Leicester Biomedical Research Centre and the NIHR Leeds Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health and Social Care. We thank the patients and staff who have supported this project. Dr. Warren J. Manning served as a Guest Editor for this manuscript. Study Management and Recruitment centres: Grant applicants: JP Greenwood (chief investiga‐ tor), GP McCann, C Berry, M Dweck, J Moon, CM Miller, A Chiribiri, S Prasad, VM Ferreira, C Bucciarelli‐Ducci, D Dawson. Data repository and statistical analysis: Glasgow Clinical Trials Unit. Senior study statistician: Prof A McConnachie, GCTU. Local Principle Investigators and Recruitment Centres: Prof John Green‐ wood, Leeds Teaching Hospitals NHS Trust, UK; Prof Gerry McCann, Glenfield Hospital, Leicester, UK; Prof Dana Dawson, Aberdeen Royal Infirmary, UK; Prof Marc Dweck, Royal Infirmary of Edinburgh, UK; Prof Vanessa Ferreira, JohnRadcliffe Hospital, Oxford, UK; Prof Colin Berry, Queen Elizabeth University Hospital, Glasgow, UK; Dr Peter Swoboda, Pinderfields Hospital, Wakefield, UK; Dr Richard Steeds, Queen Elizabeth Hospital, Birmingham, UK; Prof James Moon, UCL Hospital London, UK; Dr Christopher Miller, Wythenshawe Hospital, Manchester, UK; Dr Timothy Fairbairn, Liverpool Heart and Chest Hospital, UK; Dr Andrew Flett, Southampton General Hospital, UK; Prof Marianna Fontana, Royal Free Hospital, London, UK; Dr Thomas Green, Northumbria NHS Trust, UK; Prof Amedeo Chiribiri, St Thomas’ Hospital, London, UK; Dr Chiara Bucciarelli‐Ducci, University Hospitals Bristol and Weston NHS Trust, UK; Dr Graham Cole, Hammersmith Hospital, London, UK; Prof Sanjay Prasad, Royal Brompton Hospital, London, UK; Dr Adam McDiarmid, Freeman Hospital, New‐ castle Upon Tyne, UK; Dr Nicholas Bunce, St Georges Hospital, London, UK; Dr Prathap Kanagala, Aintree University Hospital, Liverpool, UK; Prof Nicholas Bellenger, The Royal Devon and Exeter Hospital, UK; Dr Tishi Ninan, Swansea Bay University Hospital, UK; Dr Khaled Alfakih, Lewisham University Hospital, London, UK; Prof James Moon, St Bartholomew’s Hospital, London, UK. Funding COVID‐HEART is funded by the National Institute for Health Research (NIHR) and UK Research and Innovation (UKRI) COVID‐19 Rapid Response Rolling Call (Grant Number COV0254), and sponsored by the University of Leeds, UK. The study has been endorsed by the British Society of Cardiovascular Magnetic Resonance (BSCMR) Research Group, and nationally prioritised, and received both BHF‐NIHR Cardiovascular Partnership Flagship Status, and the NIHR Urgent Public Health Group identified it as an Urgent Public Health (UPH) study. Funding for the translation of the patient information leaflets into non‐ English languages was provided by the West Yorkshire and Humber Clinical Research Network (CV070).Peer reviewedPublisher PD

Optimized T1- and T2-weighted volumetric brain imaging as a diagnostic tool in very preterm neonates.

BACKGROUND: T1- and T2-W MR sequences used for obtaining diagnostic information and morphometric measurements in the neonatal brain are frequently acquired using different imaging protocols. Optimizing one protocol for obtaining both kinds of information is valuable. OBJECTIVE: To determine whether high-resolution T1- and T2-W volumetric sequences optimized for preterm brain imaging could provide both diagnostic and morphometric value. MATERIALS AND METHODS: Thirty preterm neonates born between 24 and 32 weeks' gestational age were scanned during the first 2 weeks after birth. T1- and T2-W high-resolution sequences were optimized in terms of signal-to-noise ratio, contrast-to-noise ratio and scan time and compared to conventional spin-echo-based sequences. RESULTS: No differences were found between conventional and high-resolution T1-W sequences for diagnostic confidence, image quality and motion artifacts. A preference for conventional over high-resolution T2-W sequences for image quality was observed. High-resolution T1 images provided better delineation of thalamic myelination and the superior temporal sulcus. No differences were found for detection of myelination and sulcation using conventional and high-resolution T2-W images. CONCLUSION: High-resolution T1- and T2-W volumetric sequences can be used in clinical MRI in the very preterm brain to provide both diagnostic and morphometric information